Proteins are composed of amino acids linked together by peptide bonds. There are 20 standard amino acids that make up proteins. Amino acids have different properties depending on their side chains, which can be nonpolar, polar, acidic, or basic. When amino acids join together via peptide bonds, they form the primary structure of proteins. The peptide bond is planar and rigid, giving proteins their distinctive 3D structures.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
Finishing oxidation by looking at the Baeyer-Villiger reaction and then turning our attention to reduction. Once again we will see the usual suspects with a who is who of hydride sources.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
This document provides a summary of dienes and alkynes. It discusses resonance stabilization of conjugated dienes and their regioisomers when undergoing electrophilic addition. For alkynes, it covers their lack of acidity due to their sp hybridization and decreasing acid strength. It also summarizes the hydration of alkynes, which proceeds by a Markovnikov addition through a mercurinium ion intermediate and tautomerizes to the enol form.
The document summarizes the retrosynthetic analysis and total synthesis of the natural product callipeltoside C. The retrosynthesis breaks the molecule down into 3 main fragments - the sugar portion, middle section, and bottom half. The synthesis proceeds by synthesizing each fragment separately and coupling them together, with the sugar portion requiring the most steps due to protecting group manipulation and diastereoselective transformations. The total synthesis takes 18 linear steps to assemble all the fragments and achieve the target natural product.
The document summarizes key concepts from Lecture Seven on alkenes and alkynes. It discusses hydrogenation of alkenes and alkynes using catalysts like Pd/C, including syn and anti addition. It provides an example of the hydrogenation of resiniferatoxin. It also explains the importance of stereochemistry in hydrogenation reactions and mechanisms of addition. Partial hydrogenation reactions using Lindlar catalyst or Na/NH3 are described. The mechanism of radical additions is shown.
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
The big topic of the last few years, the use of small organic molecules to catalyse enantioselective transformations. This lecture will start with proline before moving on to some of MacMillan's contributions to this field and, finally, finish with hydrogen bond catalysts and Brønsted acids.
Finishing oxidation by looking at the Baeyer-Villiger reaction and then turning our attention to reduction. Once again we will see the usual suspects with a who is who of hydride sources.
Self explanatory really, this lecture looks at chiral auxiliaries. We will concentrate on oxazolidinones in alkylations, aldol reaction and the Diels-Alder reaction. There will be a couple examples of other auxiliaries.
This document provides a summary of dienes and alkynes. It discusses resonance stabilization of conjugated dienes and their regioisomers when undergoing electrophilic addition. For alkynes, it covers their lack of acidity due to their sp hybridization and decreasing acid strength. It also summarizes the hydration of alkynes, which proceeds by a Markovnikov addition through a mercurinium ion intermediate and tautomerizes to the enol form.
The document summarizes the retrosynthetic analysis and total synthesis of the natural product callipeltoside C. The retrosynthesis breaks the molecule down into 3 main fragments - the sugar portion, middle section, and bottom half. The synthesis proceeds by synthesizing each fragment separately and coupling them together, with the sugar portion requiring the most steps due to protecting group manipulation and diastereoselective transformations. The total synthesis takes 18 linear steps to assemble all the fragments and achieve the target natural product.
The document summarizes key concepts from Lecture Seven on alkenes and alkynes. It discusses hydrogenation of alkenes and alkynes using catalysts like Pd/C, including syn and anti addition. It provides an example of the hydrogenation of resiniferatoxin. It also explains the importance of stereochemistry in hydrogenation reactions and mechanisms of addition. Partial hydrogenation reactions using Lindlar catalyst or Na/NH3 are described. The mechanism of radical additions is shown.
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
The document discusses the concept of substrate control in directed epoxidation reactions. It shows that when performing epoxidation reactions on substrates containing multiple oxidizable positions, the reaction preferentially forms epoxides at positions that minimize 1,3-allylic strain. Substrate control allows for high regioselectivity in epoxidation based on sterics and substrate conformation. Directed epoxidation reactions can achieve up to 99:1 regioselectivity through substrate control and transition state stabilization.
This document summarizes reactions of alkenes including:
1. Addition of bromine to form bromonium ions and give anti-addition of bromine with stereospecificity.
2. Diol formation from epoxide ring opening, KMnO4 oxidation, and hydroboration-hydration which can give stereospecific or racemic mixtures.
3. Examples of biologically active natural products formed from alkene reactions like epothilones and dynemicin A.
The document provides information about various carbon-carbon bond forming reactions including the aldol reaction, Claisen condensation, Dieckmann cyclization, Robinson annulation, and the Hajos-Parrish-Eder-Sauer-Wiechert reaction. It discusses how to control the chemoselectivity of reactions and outlines strategies like choosing the correct nucleophile or pre-forming enolates. Functional groups in specific arrangements like a 1,3-diol relationship indicate certain reaction types. The key message is that retrosynthesis involves recognizing underlying patterns in molecular structures.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The lecture discusses the mechanisms of ozonolysis and radical addition reactions to alkenes. Ozonolysis involves a three step mechanism where ozone cleaves the alkene to form an ozonide intermediate which then decomposes to a carbonyl compound. Radical addition reactions involve a three step chain reaction mechanism of initiation, propagation, and termination. The stability of radical intermediates is influenced by resonance stabilization, which explains why styrene reacts with HBr to give a single, benzylic bromide product.
The document summarizes key concepts about alkene reactions:
1) Markovnikov addition results in the addition occurring on the carbon with the most hydrogen substituents, giving the more substituted primary carbocation which is most stable.
2) Hydroboration follows anti-Markovnikov addition, with the BH3 group adding to the less substituted carbon. Oxidation then occurs with H2O2/NaOH through a 1,2-shift to give anti-Markovnikov addition.
3) Organoboranes are unstable and hydroboration involves coordination of BH3 to the alkene, allowing for stereospecific anti-Markovnikov addition
1) The document discusses molecular conformations, which are different shapes of the same molecule caused by bond rotation.
2) Ethane is used as a simple example to illustrate how the energy of a molecule changes with dihedral angle. The staggered conformation is lowest in energy while the eclipsed conformation is highest.
3) Butane is a more complex example with multiple rotatable bonds, leading to four important conformations based on whether groups are staggered or eclipsed. The anti-periplanar staggered conformation is preferred with no strain, while syn-periplanar eclipsed has the most strain.
This document summarizes the optimization of an organocatalytic domino Michael-Aldol reaction to synthesize bispirooxindoles. Various cinchona alkaloid derivatives were evaluated as catalysts, with a trifunctional S-binaphthyl diamine catalyst (VIII) giving excellent diastereoselectivity and enantioselectivity. Reaction conditions such as temperature, solvent, and substrate scope were varied, demonstrating good yields and selectivity for a range of substrates. A different protecting group was also investigated, and bispirooxindoles were successfully deprotected to give the corresponding amines in high yields and selectivity.
This document discusses functional group interconversions, specifically focusing on sulfonate esters. It provides information on common sulfonate leaving groups like tosyl, mesyl, and triflate groups and their relative reactivities. It also discusses the mechanisms and standard methods for preparing sulfonate esters from alcohols using these strong acidic leaving groups, noting that pyridine cannot deprotonate an alcohol directly due to pKa differences.
The racemic dibromide undergoes an E2 elimination with pyridine as the base to give the trans product selectively. This is because the anti-periplanar conformation required for E2 is favored for one enantiomer due to less steric interaction between the phenyl groups.
The meso dibromide cannot undergo such a stereospecific E2 reaction. Instead, it undergoes a thermally allowed homolytic cleavage of the weaker C-Br bond to eliminate Br2. This reaction does not require a particular transition state geometry.
Alcohols and ethers contain the C-O functional group. Alcohols have an O-H bond while ethers do not. The C-O bond in alcohols and ethers is inert to heterolytic cleavage but can undergo substitution reactions under acidic conditions via protonation of the oxygen. Ether chemistry follows similar mechanisms to alcohol chemistry involving C-O bond cleavage and substitution. Alcohols can act as weak acids via protonation of the O-H bond or as nucleophiles. Common reactions of alcohols include oxidation to form carbonyl compounds, conversion of the O-H to a better leaving group followed by substitution, and elimination reactions to form alkenes
Told you that this was the important one. This weeks reagents include more enolates and then reactions with the C=O group including the such classics as the Wittig reaction.
Finishing off the reactions of carboxylic acid derivatives (well the substitution reactions) and introducing oxidation and reduction. Then looking at the oxidation of alkenes (epoxidation and dihydroxylation) and alcohols (the usual suspects).
Lecture 6: C-C bond formation
The big one; the all important formation of C-C bonds. Reagents include organometallics and enolates. There will also be a slight detour into the wonderful world of pKa.
This chapter outline discusses DNA and RNA structure and function, including:
- The discovery that DNA is the genetic material through experiments with viruses.
- The double helix structure of DNA determined by Watson and Crick based on data from Franklin and others.
- DNA replication through semiconservative replication to produce identical copies.
- Transcription of DNA to mRNA and the three types of RNA (mRNA, tRNA, rRNA).
- Translation of mRNA using tRNA to specify amino acid sequence and produce proteins according to the genetic code.
BITS - Introduction to Mass Spec data generationBITS
Mass spectrometry is a technique that analyzes molecules based on their mass-to-charge ratio. It involves ionizing samples using sources like MALDI or ESI, separating the ions using mass analyzers like time-of-flight or quadrupole, and detecting the ions. Tandem mass spectrometry allows targeted fragmentation of selected ions to gain additional structural information. Amino acids are the building blocks of proteins and contain variable side chains attached to a common peptide backbone. Mass spectrometry is useful for analyzing proteins and peptides.
1) Electrophilic and nucleophilic aromatic substitution reactions can occur on both carbon and nitrogen atoms in heterocycles, with positions of reactivity depending on ring size and substitution.
2) Directed metalation techniques like lithiation and Grignard reactions allow for functionalization of heterocycles at specific positions. Metal derivatives can then undergo cross-coupling, substitution, or other transformations.
3) Five-membered rings are generally more reactive than six-membered rings towards electrophiles due to their electron-rich nature. The reverse is true for nucleophilic aromatic substitution.
This document provides an overview of microbial genetics, including definitions of key terms like genes, genomes, genotypes, and phenotypes. It describes DNA as a double-stranded polymer made of nucleotides that carries genetic information. The flow of genetic information involves DNA being replicated semiconservatively then transcribed into RNA, with key enzymes like DNA and RNA polymerase involved in these processes. Figures and tables illustrate DNA structure, replication, transcription, and RNA processing in eukaryotes.
Gives an introduction to total synthesis and why we do it (which reminds me, I must add a picture of Everest, as I think the fact that 'it is there' is the main reason for most syntheses). Then to introduce the topic with a reasonably simple synthesis, we will look at an example of the synthesis of Tamiflu.
The document discusses the concept of substrate control in directed epoxidation reactions. It shows that when performing epoxidation reactions on substrates containing multiple oxidizable positions, the reaction preferentially forms epoxides at positions that minimize 1,3-allylic strain. Substrate control allows for high regioselectivity in epoxidation based on sterics and substrate conformation. Directed epoxidation reactions can achieve up to 99:1 regioselectivity through substrate control and transition state stabilization.
This document summarizes reactions of alkenes including:
1. Addition of bromine to form bromonium ions and give anti-addition of bromine with stereospecificity.
2. Diol formation from epoxide ring opening, KMnO4 oxidation, and hydroboration-hydration which can give stereospecific or racemic mixtures.
3. Examples of biologically active natural products formed from alkene reactions like epothilones and dynemicin A.
The document provides information about various carbon-carbon bond forming reactions including the aldol reaction, Claisen condensation, Dieckmann cyclization, Robinson annulation, and the Hajos-Parrish-Eder-Sauer-Wiechert reaction. It discusses how to control the chemoselectivity of reactions and outlines strategies like choosing the correct nucleophile or pre-forming enolates. Functional groups in specific arrangements like a 1,3-diol relationship indicate certain reaction types. The key message is that retrosynthesis involves recognizing underlying patterns in molecular structures.
A look at epothilone A as it includes examples of many different forms of asymmetric synthesis. Also includes a little bit about ring-closing metathesis.
The lecture discusses the mechanisms of ozonolysis and radical addition reactions to alkenes. Ozonolysis involves a three step mechanism where ozone cleaves the alkene to form an ozonide intermediate which then decomposes to a carbonyl compound. Radical addition reactions involve a three step chain reaction mechanism of initiation, propagation, and termination. The stability of radical intermediates is influenced by resonance stabilization, which explains why styrene reacts with HBr to give a single, benzylic bromide product.
The document summarizes key concepts about alkene reactions:
1) Markovnikov addition results in the addition occurring on the carbon with the most hydrogen substituents, giving the more substituted primary carbocation which is most stable.
2) Hydroboration follows anti-Markovnikov addition, with the BH3 group adding to the less substituted carbon. Oxidation then occurs with H2O2/NaOH through a 1,2-shift to give anti-Markovnikov addition.
3) Organoboranes are unstable and hydroboration involves coordination of BH3 to the alkene, allowing for stereospecific anti-Markovnikov addition
1) The document discusses molecular conformations, which are different shapes of the same molecule caused by bond rotation.
2) Ethane is used as a simple example to illustrate how the energy of a molecule changes with dihedral angle. The staggered conformation is lowest in energy while the eclipsed conformation is highest.
3) Butane is a more complex example with multiple rotatable bonds, leading to four important conformations based on whether groups are staggered or eclipsed. The anti-periplanar staggered conformation is preferred with no strain, while syn-periplanar eclipsed has the most strain.
This document summarizes the optimization of an organocatalytic domino Michael-Aldol reaction to synthesize bispirooxindoles. Various cinchona alkaloid derivatives were evaluated as catalysts, with a trifunctional S-binaphthyl diamine catalyst (VIII) giving excellent diastereoselectivity and enantioselectivity. Reaction conditions such as temperature, solvent, and substrate scope were varied, demonstrating good yields and selectivity for a range of substrates. A different protecting group was also investigated, and bispirooxindoles were successfully deprotected to give the corresponding amines in high yields and selectivity.
This document discusses functional group interconversions, specifically focusing on sulfonate esters. It provides information on common sulfonate leaving groups like tosyl, mesyl, and triflate groups and their relative reactivities. It also discusses the mechanisms and standard methods for preparing sulfonate esters from alcohols using these strong acidic leaving groups, noting that pyridine cannot deprotonate an alcohol directly due to pKa differences.
The racemic dibromide undergoes an E2 elimination with pyridine as the base to give the trans product selectively. This is because the anti-periplanar conformation required for E2 is favored for one enantiomer due to less steric interaction between the phenyl groups.
The meso dibromide cannot undergo such a stereospecific E2 reaction. Instead, it undergoes a thermally allowed homolytic cleavage of the weaker C-Br bond to eliminate Br2. This reaction does not require a particular transition state geometry.
Alcohols and ethers contain the C-O functional group. Alcohols have an O-H bond while ethers do not. The C-O bond in alcohols and ethers is inert to heterolytic cleavage but can undergo substitution reactions under acidic conditions via protonation of the oxygen. Ether chemistry follows similar mechanisms to alcohol chemistry involving C-O bond cleavage and substitution. Alcohols can act as weak acids via protonation of the O-H bond or as nucleophiles. Common reactions of alcohols include oxidation to form carbonyl compounds, conversion of the O-H to a better leaving group followed by substitution, and elimination reactions to form alkenes
Told you that this was the important one. This weeks reagents include more enolates and then reactions with the C=O group including the such classics as the Wittig reaction.
Finishing off the reactions of carboxylic acid derivatives (well the substitution reactions) and introducing oxidation and reduction. Then looking at the oxidation of alkenes (epoxidation and dihydroxylation) and alcohols (the usual suspects).
Lecture 6: C-C bond formation
The big one; the all important formation of C-C bonds. Reagents include organometallics and enolates. There will also be a slight detour into the wonderful world of pKa.
This chapter outline discusses DNA and RNA structure and function, including:
- The discovery that DNA is the genetic material through experiments with viruses.
- The double helix structure of DNA determined by Watson and Crick based on data from Franklin and others.
- DNA replication through semiconservative replication to produce identical copies.
- Transcription of DNA to mRNA and the three types of RNA (mRNA, tRNA, rRNA).
- Translation of mRNA using tRNA to specify amino acid sequence and produce proteins according to the genetic code.
BITS - Introduction to Mass Spec data generationBITS
Mass spectrometry is a technique that analyzes molecules based on their mass-to-charge ratio. It involves ionizing samples using sources like MALDI or ESI, separating the ions using mass analyzers like time-of-flight or quadrupole, and detecting the ions. Tandem mass spectrometry allows targeted fragmentation of selected ions to gain additional structural information. Amino acids are the building blocks of proteins and contain variable side chains attached to a common peptide backbone. Mass spectrometry is useful for analyzing proteins and peptides.
1) Electrophilic and nucleophilic aromatic substitution reactions can occur on both carbon and nitrogen atoms in heterocycles, with positions of reactivity depending on ring size and substitution.
2) Directed metalation techniques like lithiation and Grignard reactions allow for functionalization of heterocycles at specific positions. Metal derivatives can then undergo cross-coupling, substitution, or other transformations.
3) Five-membered rings are generally more reactive than six-membered rings towards electrophiles due to their electron-rich nature. The reverse is true for nucleophilic aromatic substitution.
This document provides an overview of microbial genetics, including definitions of key terms like genes, genomes, genotypes, and phenotypes. It describes DNA as a double-stranded polymer made of nucleotides that carries genetic information. The flow of genetic information involves DNA being replicated semiconservatively then transcribed into RNA, with key enzymes like DNA and RNA polymerase involved in these processes. Figures and tables illustrate DNA structure, replication, transcription, and RNA processing in eukaryotes.
The document discusses the main types of biological macromolecules - proteins, carbohydrates, lipids, and nucleic acids. It provides details on their structures, functions and examples of each type of macromolecule. The key macromolecules discussed are amino acids that make up proteins, monosaccharides and polysaccharides that make up carbohydrates, triglycerides and phospholipids that make up lipids, and nucleotides that make up DNA and RNA nucleic acids.
The document discusses several DNA repair mechanisms including mismatch repair, base excision repair, nucleotide excision repair, direct repair, and recombinational repair. It also describes different types of recombination including homologous recombination, site-specific recombination, and transposition. Finally, it discusses mechanisms of meiotic recombination including gene conversion and resolution of Holliday structures.
Foreign DNA and vector DNA are cut with restriction enzymes, leaving sticky ends. The DNA fragments are then ligated together. Host cells take up the recombinant DNA and propagate it. Libraries contain fragments of DNA from a source inserted into vectors. Genomic libraries contain chromosomal DNA fragments, while cDNA libraries contain mRNA sequences converted to DNA. Expression libraries contain cDNAs in vectors allowing protein expression.
Proteins are composed of amino acids linked by peptide bonds. There are four levels of protein structure: primary, secondary, tertiary, and quaternary. The primary structure is the linear sequence of amino acids. Secondary structures form based on hydrogen bonding patterns between amino acids. The two main secondary structures are the alpha helix, where amino acids coil into a helical shape, and the beta sheet, where amino acids align into beta strands connected by hydrogen bonds.
Proteins are composed of amino acids linked by peptide bonds. There are four levels of protein structure - primary, secondary, tertiary, and quaternary. The primary structure is the linear sequence of amino acids. The two most common types of secondary structure are the alpha helix and beta sheet. In an alpha helix, amino acid residues form a coil stabilized by hydrogen bonds between residues four places apart in the sequence. In a beta sheet, residues form extended zigzag patterns stabilized by hydrogen bonds between residues on adjacent strands running in parallel or anti-parallel directions.
Proteins are composed of amino acids linked by peptide bonds. They have four levels of structure - primary, secondary, tertiary, and quaternary. The primary structure is the amino acid sequence. Common secondary structures are alpha helices and beta sheets formed by hydrogen bonding between amino acids. Tertiary structure refers to the overall 3D structure formed from secondary structures. Quaternary structure involves interactions between multiple polypeptide subunits.
The primary structure of a protein refers to the specific sequence of amino acids in the protein chain linked together by peptide bonds. The unique amino acid sequence determines how the protein folds into its 3D structure and performs its function. While different sequences can result in very different protein shapes and functions, the sequence is precisely determined by the mRNA template which is transcribed from DNA.
Proteins are composed of amino acids linked by peptide bonds. They have four levels of structure - primary, secondary, tertiary, and quaternary. The primary structure is the amino acid sequence. Secondary structures include alpha helices and beta sheets formed by hydrogen bonding. Tertiary structure is the overall 3D shape formed by interactions between secondary structures. Quaternary structure refers to the arrangement of multiple polypeptide subunits in a protein.
Aldehydes and ketones are important functional groups that contain a carbonyl group (C=O). Aldehydes and ketones can undergo nucleophilic addition reactions, where nucleophiles attack the electrophilic carbonyl carbon. When aldehydes and ketones react with water in the presence of an acid catalyst, they form unstable hydrates that readily revert back to the original carbonyl compound. Alcohols can also add to the carbonyl group to form stable hemiacetals and acetals. Aldehydes readily undergo oxidation reactions to form carboxylic acids, while ketones are more resistant to oxidation.
The Arbuzov reaction is the nucleophilic substitution reaction of a trialkylphosphite with an alkyl halide to form a trialkylphosphite ester.
The general reaction is:
ROPO(OR')2 + R'X → ROP(O)(OR')OR' + X-
Where R and R' can be alkyl groups of varying size.
The reaction proceeds through an S N2 mechanism. The trialkylphosphite acts as a nucleophile, with the phosphoryl oxygen attacking the electrophilic carbon of the alkyl halide. This occurs with inversion of configuration at the carbon.
The leaving group, X-, departs, forming the trialkylphosphite est
This is the biggy, the one everyone wants to achieve. Here we will be looking at metal-based chiral catalysis. We will concentrate on bisoxazoline-based Lewis acid catalysis and then look at reductions before finishing with the ubiquitous Sharpless epoxidation and dihydroxylation.
This document discusses stereochemistry and stereoisomers. It defines stereoisomers as isomers that have the same molecular formula and connectivity but differ in the three-dimensional arrangement of atoms. There are two main types of stereoisomers - enantiomers, which are nonsuperimposable mirror images of each other, and diastereomers, which are not mirror images. Chirality and how compounds interact with polarized light are also explained. The Cahn-Ingold-Prelog system for assigning R and S configurations to chiral centers is described. Examples are provided to illustrate key stereochemistry concepts.
This document discusses the antibiotic tetracycline. It belongs to a group of antibiotics called tetracyclines which are obtained through fermentation of Streptomyces bacteria. Tetracycline has a complex stereochemistry and exists as a zwitterion. It works by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. It is stable under acidic conditions but forms anhydrotetracycline, while under basic conditions it opens to form isotetracycline. It forms insoluble chelates with metals. Tetracycline has broad-spectrum activity against many gram-positive and gram-negative bacteria.
This document provides information about the 20 standard amino acids. It discusses their basic structures, including the central α-carbon and α-amino and α-carboxyl groups. It also classifies the amino acids based on the polarity of their side chains into hydrophobic/non-polar, polar, and charged groups. Additionally, it shows the structures of representative amino acids from each group.
The alkane with the highest boiling point is likely to be E, CH3CH2CH2CH2CH2CH3. This is because it is a straight chain alkane with the longest carbon chain length. Straight chain alkanes have stronger intermolecular van der Waals' forces compared to branched chain alkanes due to their more compact packing. This results in higher boiling points for straight chain alkanes.
Serine proteases are digestive enzymes like trypsin, chymotrypsin, and elastase that differ in substrate specificity. Their catalytic mechanism involves a catalytic triad of serine, histidine, and aspartate residues. During catalysis, the serine hydroxyl performs a nucleophilic attack on the substrate peptide bond, forming a transient acyl-enzyme intermediate before hydrolysis releases the cleaved peptides. Chymotrypsin prefers substrates with aromatic or large hydrophobic residues at the cleavage site.
The document discusses various types of lipids including fatty acids, triglycerides, phospholipids, glycolipids, and steroids. It provides classifications and examples of each type. Key points covered include essential fatty acids, fatty acid structures, triglyceride reactions, phospholipid structures and functions, glycolipid structures, steroid structures like cholesterol, and prostaglandin structures. Health effects of lipids are also summarized such as risks of saturated and trans fats.
The document discusses the stability of pharmaceutical formulations. It defines stability as a formulation remaining within its physical, chemical, microbiological, therapeutic and toxicological specifications. Stability is important to ensure drug products maintain quality and intended effects until expiration. Chemical and physical degradation pathways include hydrolysis, oxidation, photodegradation, and interactions with excipients or other drugs. Factors like temperature, pH, moisture, and light can affect the rate of degradation. The document focuses on hydrolysis and oxidation as two major degradation pathways and provides examples of each.
The document summarizes the pinacol-pinacolone rearrangement reaction, which converts an alcohol with two adjacent hydroxyl groups (a pinacol) into a ketone (a pinacolone) using an acid. It involves the following steps:
1) Protonation of one of the hydroxyl groups.
2) Loss of a water molecule.
3) Migration of an alkyl group to the carbocation formed.
4) Deprotonation to form the pinacolone product.
The reaction favors migration of groups that stabilize the carbocation intermediate best through resonance or inductive effects. For asymmetrical glycols, the group on the opposite side of
The document discusses several rearrangement reactions including the pinacol rearrangement, Beckmann rearrangement, Heck reaction, ozonolysis, and Grignard reaction. The pinacol rearrangement involves the acid-catalyzed rearrangement of vicinal diols to ketones or aldehydes. The Beckmann rearrangement converts ketoximes to N-substituted amides. The Heck reaction is a palladium-catalyzed coupling of aryl or alkenyl halides with alkenes. Ozonolysis uses ozone to cleave alkenes and alkynes, replacing the multiple bond with a carbonyl. Grignard reagents are important in organic synthesis.
The document discusses macromolecules called polymers that are composed of smaller molecules called monomers. There are three main classes of polymers in living things: carbohydrates, proteins, and nucleic acids. Carbohydrates include sugars and their polymers. Examples of sugars are monosaccharides like glucose and fructose. Carbohydrate polymers include starch, a polymer of glucose found in plants for energy storage, and glycogen, a glucose polymer that stores energy in animals. Proteins and nucleic acids are also important macromolecules composed of monomers.
The document discusses stereochemistry and the different types of isomers. It provides examples of carvone isomers that have different smells due to their molecular shapes interacting differently with receptors. Geometrical isomers in alkenes can have groups on the same or opposite sides of the double bond. The E/Z system designates whether the highest priority groups are on the same (Z) or opposite (E) sides. Conformational isomers in ethane result from free rotation around the carbon-carbon bond, with the staggered conformation being more stable.
The document discusses several types of isomerism including structural isomers, stereoisomers, and optical isomers. It provides examples to illustrate structural isomers like positional and functional isomers. Stereoisomers include geometric isomers (cis-trans), optical isomers arising from chiral carbons, and diastereomers which are stereoisomers that are not mirror images. The document also discusses properties of meso compounds and uses Fischer projections to depict stereochemistry. Common organic reactions like substitution, addition, elimination, and oxidation are briefly overviewed with examples.
The document discusses genome assembly and finishing processes. It begins by outlining typical project goals of completely restoring the genome and producing a high-quality consensus sequence. It then describes the evolution of sequencing technologies from Sanger to newer platforms and their impact on draft assemblies. Key steps in the assembly and finishing process include library preparation, assembly, identifying gaps, and improving consensus quality.
The cell membrane separates the intracellular components of the cell from the external environment. It is composed of a lipid bilayer with embedded proteins and acts as a selective barrier. The cytoplasm contains organelles that carry out specialized functions like the mitochondria, which generates energy, and the endoplasmic reticulum and Golgi apparatus, which modify and transport proteins. Lysosomes contain enzymes that break down materials inside and outside the cell. Together, these organelles and their membranes comprise the endomembrane system, which manufactures components and transports materials within the cell.
The document discusses gene expression and regulation in eukaryotes. It covers several key points in 3 sentences:
Eukaryotic genes require complex regulatory systems involving chromatin remodeling and transcription factors to initiate expression, unlike bacterial genes which can be transcribed without regulatory proteins. Development in multicellular organisms is controlled by signaling between cells using hormones and diffusible receptors which act as transcriptional regulators. Gene expression patterns in fruit flies establish polarity, segment the body, and determine segment identities through maternal, segmentation, and homeotic genes, providing insights into human developmental gene regulation.
Proteins are composed of amino acids linked together by peptide bonds to form polypeptide chains. There are 20 standard amino acids that make up proteins. Proteins have four levels of structure - primary, secondary, tertiary, and quaternary. The primary structure is the linear sequence of amino acids. Secondary structures form due to hydrogen bonding between amino acids and include alpha helices and beta sheets. Tertiary structure involves folding of secondary structures into a compact 3D structure. Hydrogen bonds, disulfide bridges, and hydrophobic interactions stabilize tertiary structure.
The document discusses several DNA repair mechanisms including mismatch repair, base excision repair, nucleotide excision repair, direct repair, and recombinational repair. It also describes different types of recombination including homologous recombination, site-specific recombination, and transposition. Finally, it discusses mechanisms of meiotic recombination including gene conversion and resolution of Holliday structures.
The document discusses chromosomes, mitosis, meiosis, and apoptosis. It explains that chromosomes contain DNA and genes, and replicate during cell division. Mitosis produces genetically identical cells while meiosis creates gametes with half the number of chromosomes. Apoptosis is programmed cell death that occurs through caspase activation and DNA fragmentation, while necrosis results from external damage.
The document discusses metabolism and metabolic pathways. It summarizes that catabolism provides energy and building blocks for anabolism through metabolic pathways. Metabolic pathways involve enzymatically catalyzed reactions, with enzymes determining the pathways. Reaction rates are influenced by factors like temperature, pH, substrate concentration, and inhibitors. The document then discusses specific metabolic pathways like glycolysis, the Krebs cycle, and the electron transport chain which are involved in breaking down carbohydrates to release energy through cellular respiration.
The document discusses the main types of biological macromolecules - proteins, carbohydrates, lipids, and nucleic acids. It provides details on their structures, functions and examples of each type of macromolecule. The key macromolecules discussed are proteins, which are composed of amino acids, and nucleic acids like DNA and RNA, which provide genetic instructions and are made of nucleotides containing nitrogen bases. Energy production in cells is also summarized, with ATP being generated through substrate-level phosphorylation or chemiosmosis using electron transport chains.
Globular proteins are spherical proteins that contain heme as a prosthetic group. Globular heme proteins function as electron carriers, parts of enzyme active sites, and carriers of oxygen and carbon dioxide like hemoglobin and myoglobin. Myoglobin stores oxygen in muscle cells and facilitates oxygen transport between hemoglobin and cells. Hemoglobin transports oxygen in red blood cells through a cooperative binding mechanism between its four heme groups that allows for high oxygen affinity when oxygen levels are high. Both proteins bind oxygen reversibly to their heme groups through interactions with proximal and distal histidine residues.
Cloning involves inserting foreign DNA into a vector, which is then taken up by host cells. The host cells replicate, producing multiple copies of the recombinant DNA. Libraries contain fragments of DNA from a source inserted randomly into vectors. Genomic libraries contain chromosomal DNA fragments, while cDNA libraries contain mRNA sequences converted to DNA. Expression libraries contain cDNAs in vectors allowing protein expression. Cloning allows isolation and expression of genes, enabling study and production of proteins.
The document summarizes various genetic techniques including PCR, restriction mapping, the human genome project, in situ hybridization, and cloning the gene responsible for alkaptonuria. It provides an example of how PCR, genomic libraries, DNA sequencing, and other methods were used to clone the HGO gene involved in alkaptonuria. Ethical considerations are discussed around using genetic testing to predict late-onset genetic disorders in fetuses.
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2. Amino acids-proteins
• I. Overview
• Most diverse and abundant molecules in living
systems
• Functional components: enzymes, hormones, cell-
surface receptors
• Structural components: cell membranes, organelles;
bone, skin, muscle, connective tissue
• Other specialized roles: immunoglobulins,
hemoglobin, albumin
3.
4. II. Structure of Amino Acids
• More than 300 amino acids known, but only 20 coded
for by DNA
• At pH 7.4 (physiological pH), amino acids exist in
zwitterionic form (positive NH3+ and negative COO-
charges).
• Classified based on side chain (R) group:
Nonpolar, Polar, Charged (acidic or basic)
5.
6.
7. A. Amino acids with non-polar side chains
• do not bind nor give protons
• do not form hydrogen bonds
• have hydrophobic interactions
• 1. Location of non-polar (hydrophobic) amino acids in
proteins
– In soluble proteins (aqueous environment), found in
the interior of proteins (shielded from environment)
– In membranes or other hydrophobic
environments, found on protein surface.
– Proline: side chain forms an imino group
11. • 0 charge at neutral pH
• Cys & Tyr can lose a proton at alkaline pH
• Ser, Thr & Tyr – polar –OH can form hydrogen
bonds
• Asn & Gln contain –COOH (carboxy) and –
CONH2 (carboxyamine) groups – can form
hydrogen bonds.
12.
13. • 1. Disulfide bond:
• Side chain of Cys contains –SH group –
important active site of enzymes
• Proteins with 2 –SH groups can form a
disulphide bridge or cystine dimer (-S-S- ,
intermolecular or intramolecular).
14.
15. B. Amino acids with uncharged polar side chains
• 2. Side chains as sites of attachments for other
compounds:
• Ser, Thr & Tyr contain polar –OH group – site of
attachment for PO4- group, for e.g. Ser side-
chain important active site component in many
enzymes
– -CONH2 group of Asn and –OH group of Ser &
Thr serve as site of attachment of
oligosaccharide chains in glycoproteins
16.
17. C. Amino acids with acidic side chains
• Asp & Glu are proton donors.
• At neutral pH (physiological), side chains fully
ionized or dissociated (COO-) and carry a net
negative charge.
• Contribute a negative charge to proteins .
• Aspartate (aspartic acid) and glutamate
(glutamic acid).
• R groups typically have a pK< 7
18.
19.
20.
21. D. Amino acids with basic side chains
• Side chains of basic amino acids accept protons
• At physiologic pH, side chains of Lys and Arg are fully ionized –
positively charged ( NH3+)
• Contribute a positive charge to proteins that contain them
• Have a pK value>7
( histones have an abundance of Arg and lys, net +ve charge)
• His -- weakly basic and partially positively charged at
physiologic pH- good buffering capacity
• In proteins, can be +ve or –ve depending on environment of
protein (important role in proteins like myoglobin).
22.
23. E. Abbreviations and symbols for commonly occurring amino acids
3-letter abbreviation and one-letter symbol
1. Unique first letter
Cys C
Cysteine
Histidine His H
Isoleucine Ile I
Methionine Met M
Serine Ser S
Valine Val V
24. 2. Most commonly occurring amino acids have priority
Ala A
Alanine
Glycine Gly G
Leucine Leu L
Proline Pro P
Threonine Thr T
25. 3. Similar sounding names
Arg R (“aRginine)
Arginine
Asparagine Asn N (contains N)
Aspartate Asp D (“asparDic”)
Glutamate Glu E (“glutEmate”)
Glutamine Gln Q (“Q-tamine”)
Phenylalani Phe F (“Fenylalanine”)
ne
Tyrosine Tyr Y (“tYrosine”)
Tryptophan Trp W (double ring in the
molecule)
26. 4. Letter close to initial letter:
Asx B
Aspartate or
asparagines
Glutamate or Glx Z
glutamine
Lysine Lys K (near L)
Undetermined X
amino acid
27.
28. F. Optical properties of amino acids:
• α-C of each amino acid attached to 4 different
chemical groups
• α-C is chiral or optically active i.e. it has four
different groups attached to the -carbon
(except Gly). The number of optical isomers is
2n, where n is the number of chiral atoms in the
molecule.
• 2 stereoisomers, optical isomers or
enantiomers: D- and L- forms are mirror images
of one another, only L-forms found in human
bodies
29.
30.
31. I. Overview
• 20 amino acids linked
together with peptide
bonds
• 4 organizational levels:
primary, secondary,
tertiary and quaternary
36. Peptide Bond
• Not broken when
proteins are
denatured
• Prolonged exposure to
acid or base at high
temps is necessary to
break bonds.
37.
38. • 1. Naming the peptide
• a. order of amino acids in a peptide
• Left (N-terminal a.a.) is written first, C-terminal next
• b. Naming of polypeptides
• component a.a. in peptides called moieties or
residues.
• Except C-terminal, all moieties called –yl instead of –
ine –ate, or -ic
• E.g. valylglycylleucine
39. Characteristics of the peptide bond:
• a. Lack of rotation around the bond:
• partial double bond- rigid and planar. bond
between -C and -amino or –CO group is
rotatable
• b. Trans configuration:
• (steric interference in cis position)
• c. Uncharged but polar:
• like all –CONH2 links, peptide bonds do not
protonate between pH 2-12
• only side chains and N- and C- terminals can ionize
• peptide bond is polar (uncharged) and can be
involved in H-bonding.
41. A peptide bond is formed from a condensation reaction (dehydration) involving two
amino acids.
A molecule of H2O is eliminated.
42. Dipeptide formation
H
H H O
O N C C
H
H3N C C O
H CH
O
CH3
H3C CH3
alanine valine
H2O
peptide bond
H O H
O
amino carboxyl
H3N C C N C C
terminus terminus
H O
( amino group) CH3 CH
H3C CH3
alaninylvaline
44. Characteristics of the peptide bond
H O H
O
1. partial double-bond character
H3N C C N C C
• due to resonance H O
R1 R2
O R2 O R2
H H
C C O C C O
C N C C
C N
H3N H H3N H
H O H O
R1 R1
O R2
H
C C O
C C
N
H3N H
H O
R1
45. Characteristics of the peptide bond
2. rigid and planar
• rotation occurs around single bonds but not around double bonds
no rotation around
peptide bond
H O H
O
H3N C C N C C
H O
R1 R2
46. O
O H
C
Rotation around single bonds H
C C
O
C N R2
H3N
H
R1
Because no rotation is possible around O R2
double bonds, the stereochemistry of the
H
peptide bond is fixed. C C O
C N C
H3N H
H O
R1
O R2
R1
C C O
H
C N C
H
H O
NH3
47. Characteristics of the peptide bond
4. Uncharged but polar
• dipole moment exists due to separation of charge
O R2
H
C C O
C C
N
H3N H
H O
R1
48. Characteristics of the peptide bond - summary
• partial double bond character
• rigid and planar
• trans configuration
• uncharged but polar
amide
trans plane
config
O R2
H
C C O
C N C
H3N H
H O
R1
49. B. Determination of the amino acid
composition of a polypeptide
• First, identify and quantify constituent amino acids.
• Pure sample must be used, contamination gives
errors.
• 1. Acid hydrolysis:
• Hydrolyzed by strong acid at 110 C for 24 h
• Peptide bonds cleaved
• Gln & Asn Glu & Asp; Trp mostly destroyed
• Procedure gives composition but not sequence
50. • 2. Chromatography:
• Individual aa’s separated by cation-exchange chromatography
• Anion-exchange resin for -vely charged aa’s
• Eluted from column by buffers of increasing ionic strength and pH
• aa’s separated at different ionic strength and pH
• 3. Quantitative analysis:
• Quantified with ninhydrin purple compd. with amino acids, NH3
and amines (yellow color with imino group of Pro).
• Intensity of color measured in spectrophotometer
• Area under curve proportional to amount of amino acid
• If MW of protein known, no. of residues of each aa
known, otherwise, only ratio of no. of molecules of each amino acid
determined.
• Done using amino acid analyzer
51.
52. C. Sequencing of the peptide from its N-terminal
end
• Phenylisothiocyanate –
Edman’s reagent – used to
label N-terminal res under
mildly alkaline conditions.
phenylthiohydantoin (PTH).
• This makes N-terminal
residue peptide bond weak;
break it without breaking
others.
• Above process occurs in a
cycle to sequence peptide
using “sequenator”
• Can be used for
polypeptides of 100 a.a. or
less.
53. O
H2N CH C Lys His Phe Leu Arg COOH
CH3
N C S
N-terminal 1. Labeling
Phenylisothiocyanate
alanine
(Edman’s reagent)
H
O
HN CH C Lys His Phe Leu Arg COOH
S C CH3 labeled peptide
H N 2. Acid
cyclization and expulsion of
hydrolysis
shortened peptide chain
O S
+ C
H2N CH C His Phe Leu Arg COOH N NH
(CH2)4 C CH
O
NH 2 CH3
N-terminal PTH-alanine
lysine
54. Cleavage of peptide into smaller fragments
• occurs before Edman degradation
• necessary if peptide is > 100 amino acids in length
• need to use more than one cleaving agent in order to
determine amino acid sequence
• different enzyme/chemical specificity
• overlap peptide fragments in order to determine original
sequence
55. • 2. Chemical Cleavage:
• Cyanogen bromide cleaves polypeptides on –CO side of methionine
residue
• 3. Overlapping peptides:
• Individual peptides sequenced by Edman’s degradation
• Overlapping peptides help determine sequence
• 4. Multimeric proteins:
• Multiple peptides separated (H-bonds and noncovalent bonds) by urea or
guanidine.HCl
• Disulfide bridges broken with performic acid.
58. • Secondary structures result from local
arrangement of adjacent amino acids into an
organized 3- dimensional structure.
• H-bonds are key to stabilizing these structures.
Secondary structures include:
• Helical Structures
• Beta Structure (maximally extended primary
sequence)
• Random chain (nonrepetitive)
60. Intrachain Hydrogen Bonding is important in maintaining secondary protein structure.
Here (in the α helix) the carbonyl oxygen from one amino acid is H-bonded to an alpha
nitrogen of the 4th distant amino acid in the polymer.
Hydrogen
bond
61. • 3.6 residues per turn
• R groups extend outward
helix is disrupted by:
1) P and G
2) large numbers of charged aa’s
3) aa’s with bulky R groups
63. Sheet
• “pleated”
• all peptide bond components involved in H-bonding
• strands visualized as broad arrows
N terminal
C terminal
• may be parallel or antiparallel
67. -Bend
• function to reverse the direction of polypeptide
chain
• often include charged residues
• stabilized by ionic and/or H-bonds
• usually composed of 4 amino acids including Pro
and Gly
68. Supersecondary structure (motif)
• result from local folding of secondary structures
into small, discrete, commonly-observed aggregates
of secondary structures:
• loop
• corner
69. • extended super secondary structures are known as
domains
• barrel
• twisted sheet
71. • Tertiary structure is the 3 dimensional form of a
molecule resulting from distant protein-protein
interactions within the same polypeptide chain
(caused by folding of secondary structures):
Globular proteins are characterized as generally
having:
• a variety of different kinds of secondary structure
• spherical shape
• good water solubility
• a catalytic/regulatory/transport role i.e. a dynamic
metabolic function
72. • IV. Tertiary Structure of Globular Proteins
• Tertiary structure – folding of domains and final
arrangement of domains in protein
• Compact, hydrophobic side chains buried in interior
• Maximum hydrogen bonding of hydrophilic groups
within molecule
73. Fibrous proteins are characterized as generally
having:
• one dominating kind of secondary structure
(i.e. collagen helix in collagen)
• a long narrow rod-like structure
• low water solubility
• a role in determining tissue/cellular structure and
function (e.g. collagen, keratin)
75. • Domains
• Fundamental functional and 3-D structural units
of polypeptides
• >200 amino acids 2 or more domains
• folding within domain independent of folding
within other domains
• each domain has characteristics of small,
compact, globular protein
76. • 1. Disulfide bonds:
• formed from –SH groups of two
cysteine residues Cystine
• two Cys may be close by or far
away
• stabilize the protein found in
many secreted proteins
• 2. Hydrophobic interactions:
• interactions between nonpolar
side chains of amino acids in
interior of protein
77. • 3. Hydrogen bonds:
• interactions between
polar side chains
• interactions between
polar side chains and
water enhanced
solubility
• 4. Ionic interactions:
• e.g. Interaction of –COO-
of Asp with NH3+ of Lys
78. Protein folding
• Trial and error process that depends on
• Composition of side chains
• H-bonding
• Disulfide bonds
• Ionic interactions
• To result in most stable or favorable structure
• Chaperones: play a role in folding of proteins during
their synthesis (separate, enhance the rate, protect
residues).
79. Denaturation of Proteins
• Destruction of all but primary structure
• Denaturing agents: heat, organic solvents,
mechanical shearing, heavy metals,
detergents, chaotropic agents
• May be reversible or irreversible
• Loss of biological activity
80. Most proteins do not revert to their original tertiary
structures after denaturation.
Ribonuclease enzyme is an exception.
81.
82. Protein misfolding
• Spontaneous
• Mutation
• Proteolytic cleavage, e.g. accumulation of amyloid
plaques (amyloid-β) in Alzheimer’s.
• Abnomal form of tau accumulation in neufibillary
tangles of Alzheimer’s brain
• Prion disease: Creutzfeldt-Jakob disease – humans
• A protein- as a degenerative agent
83. -Sheet in fibrous (Amyloid) protein
• Amyloid protein deposited in brains of
Alzheimer’s disease patients –
twisted -pleated sheet fibrils with 3-D
structure virtually identical to silk fibrils
86. Quaternary structure consists of the association
of multimeric proteins (identical or nonidentical)
held together by one or more of the following
noncovalent interactions:
Hydrogen bonds
Hydrophobic interactions
(Van der Waals forces)
Electrostatic interactions (ionic
and/or polar)