The Combinatorial Chemistry is a scientific method in which a very large number of chemical entities are synthesized by condensing a small number of chemical compounds together in all combinations defined by a small set of chemical reactions.
Peptidomimetics are small protein-like chain designed to mimic a peptide, have no peptide bonds and MW<700D
Peptidomimetics are chemical structures derived from bioactive peptides which imitate natural molecules.
Arise either from –
Modification of an existing peptide,
By designing similar systems that mimics peptides, such as Peptoids and β-peptides.
An altered chemical structure is designed to adjust the molecular properties as, stability or biological activity.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Peptidomimetics are small protein-like chain designed to mimic a peptide, have no peptide bonds and MW<700D
Peptidomimetics are chemical structures derived from bioactive peptides which imitate natural molecules.
Arise either from –
Modification of an existing peptide,
By designing similar systems that mimics peptides, such as Peptoids and β-peptides.
An altered chemical structure is designed to adjust the molecular properties as, stability or biological activity.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
DRUG DISCOVERY
Drug Discovery without a lead
LEAD DISCOVERY/IDENTIFICATION
LEAD MODIFICATION
CONCEPT OF PRODRUGS AND SOFT DRUGS
DRUG RECEPTOR INTERACTIONS
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Sythesis of heterocyclic drugs ketoconazole and metronidazoleandhra university
A Heterocyclic compounds are those which has atoms of at least two different elements as members of its ring.
Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.
Hey students here i am attaching the powerpoint presenatation on the Receptor/enzyme-interaction and its analysis, Receptor/enzyme cavity size prediction, predicting
the functional components of cavities and the concept regarding the fragment based drug design.
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
What is QSAR?, introduction to 3D QSAR, CoMFA, CoMSIA, Case Study on CoMFA contour maps analysis and CoMSIA interactive forces between ligand and receptor, various Statistical techniques involved in QSAR
Pharmacophore Mapping and Virtual Screening (Computer aided Drug design)AkshayYadav176
Pharmacophore Mapping and Virtual Screening (Computer aided Drug design)
Concept of pharmacophore, Pharmacophore mapping, Identification of pharmacophore features and pharmacophore modeling, Conformation search used in pharmacophore mapping, Virtual screening.
This presentation is about Statistical method used in QSAR which is the part of computer aided drug design. In this slide we deals with choosing the descriptors or independent variables and validation about them .Linear Regression method, Non linear Regression method, Partial least square method, Cluster analysis, Principle component analysis.
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
Combinatorial chemistry and high throughputscreeningSaikiranKulkarni
Combinatorial chemistry is a collection of techniques which allow for the synthesis of multiple compounds at the same time.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs, By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery.
Sythesis of heterocyclic drugs ketoconazole and metronidazoleandhra university
A Heterocyclic compounds are those which has atoms of at least two different elements as members of its ring.
Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.
Hey students here i am attaching the powerpoint presenatation on the Receptor/enzyme-interaction and its analysis, Receptor/enzyme cavity size prediction, predicting
the functional components of cavities and the concept regarding the fragment based drug design.
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
What is QSAR?, introduction to 3D QSAR, CoMFA, CoMSIA, Case Study on CoMFA contour maps analysis and CoMSIA interactive forces between ligand and receptor, various Statistical techniques involved in QSAR
Pharmacophore Mapping and Virtual Screening (Computer aided Drug design)AkshayYadav176
Pharmacophore Mapping and Virtual Screening (Computer aided Drug design)
Concept of pharmacophore, Pharmacophore mapping, Identification of pharmacophore features and pharmacophore modeling, Conformation search used in pharmacophore mapping, Virtual screening.
This presentation is about Statistical method used in QSAR which is the part of computer aided drug design. In this slide we deals with choosing the descriptors or independent variables and validation about them .Linear Regression method, Non linear Regression method, Partial least square method, Cluster analysis, Principle component analysis.
SAR versus QSAR, History and development of QSAR, Types of physicochemical
parameters, experimental and theoretical approaches for the determination of
physicochemical parameters such as Partition coefficient, Hammet’s substituent
constant and Taft’s steric constant. Hansch analysis, Free Wilson analysis, 3D-QSAR
approaches like COMFA and COMSIA.
Combinatorial chemistry and high throughputscreeningSaikiranKulkarni
Combinatorial chemistry is a collection of techniques which allow for the synthesis of multiple compounds at the same time.
Combinatorial chemistry is one of the important new methodologies developed by researchers in the pharmaceutical industry to reduce the time and costs associated with producing effective and competitive new drugs, By accelerating the process of chemical synthesis, this method is having a profound effect on all branches of chemistry, but especially on drug discovery.
It is the presentation for Combinatorial Chemistry. this presentation should be helpful for B. Pharm students. It includes introduction, types, applications, advantages and disadvantages.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Combinatorial chemistry by Sunil Yadav SD Bihani College sri gangangar
1. PREPARED BY: GUIDED BY:
SUNIL YADAV Prof. Mahesh Kumar Kataria
M.Pharm HOD Department of Pharmaceutics.
Seth G. L. Bihani S. D. College of Technical Education
Institute of Pharmaceutical Sciences & Drug Research, Sri Ganganagar, Rajasthan 1
2. Combinatorial chemistry
Combinatorial chemistry (Combichem) is a collection of techniques which
allow for the synthesis of multiple compounds at the same time.
Conventional Reaction: A + B AB
Combinatorial Chemistry: A1- n + B1- n A1- n B1- n
This powerful new technology has begun to help pharmaceutical
companies to find new drug candidates quickly, save significant money in
preclinical development costs and ultimately change their fundamental
approach to drug discovery.
2
3. Need for Combichem
Problems with Traditional/Conventional Synthesis:
1 chemist 1 molecule
Can only make one molecule at a time.
Each synthesis very time consuming.
Multistep synthesis have loss at each step.
Purification of products very time-consuming between steps.
Yields can be low and produces very few molecules at a time for testing.
Slower lead generation.
Hundreds of molecules in a month are generated.
High risk of failure.
3
4. Need for Combichem
Benefits with Combinatorial Synthesis:
1 chemist multiple molecules
Can make multiple molecules at a time.
The time & cost associated with the generation & analysis of each
individual molecule is significantly less when compared to the time & cost
of an individual synthesis.
Yields can be high and produces many molecules at a time for testing.
Faster lead generation.
Thousands of molecules in a month are generated.
Low risk of failure.
Multiple molecules synthesized at a time.
4
5. Definition of Combichem
Combinatorial chemistry may be defined as the systematic and repetitive,
covalent connection of a set of different “building blocks” of varying
structures to each other to yield a large array of diverse molecular entities.
Combinatorial chemistry encompasses many strategies and processes for
the rapid synthesis of large, organized collections of compounds called
libraries. The collection is then tested for the biological activity. Finally the
active compound is identified and made in quantity as a single compound.
Thus the combinatorial chemistry approach has two phases:
1. Making a library.
2. Finding the active compound
5
6. History of Combichem
Although combinatorial chemistry has only really been taken up by the
industries since the 1990s, its roots can be seen as far back as the 1960s
when a researcher at Rockefeller University, Bruce Merrifield, developed a
way to make peptides by solid-phase synthesis.
Bruce Merrifield won the Nobel prize in chemistry in 1984 for his work on
solid-phase synthesis. During this time, automated peptide synthesizer
technology was in its infancy, and the preparation of individual peptides
was a challenge.
6
7. History of Combichem
The field in its modern dimensions only began to take shape in the 1980s,
when in 1984, research scientist H. Mario Geysen his coworker developed
a technique for synthesizing peptides on pin-shaped solid supports and in
1985, Richard Houghten developed a technique for creating peptide
libraries in tiny mesh "tea bags" by solid-phase parallel synthesis.
Another early pioneer was Dr. Árpád Furka (considered to be one of the
fathers of combinatorial synthesis) who introduced the commonly used
split-and-pool method in 1988, which is used to prepare millions of new
peptides in only a couple of days and also for synthesizing organic
libraries.
7
8. Principle of Combichem
To prepare a large number of different compounds at the same time Instead
of synthesizing compounds in a conventional one at a time manner and
then to identify the most promising compound for further development by
high throughput screening (HTS).
In combinatorial synthesis different compounds are generated
simultaneously under identical reaction conditions in a systematic manner,
so that ideally the products of all possible combinations of a given set of
starting materials (termed building blocks) will be obtained at once. The
collection of these finally synthesized compounds is referred to as a
combinatorial library. The library is then screened for useful properties and
the active compounds are identified.
8
9. Principle of Combichem
Example:
A + B AB (A) Conventional approach
A1 - n + B1 - n A1 – n B1 – n or (B) Combinatorial approach
A1 B1 A1B1 A1B2 A1Bn
A2 B2 A2B1 A2B2 A2Bn
An Bn AnB1 AnB2 AnBn
(A) In a conventional synthesis one starting material A reacts with one reagent
B resulting in one product AB.
(B) In a combinatorial synthesis different building blocks of type A (A1-An)
are treated simultaneously with different building blocks of type B (B1-Bn)
according to combinatorial principles, each starting material A reacts
separately with all reagents B resulting in a combinatorial library A1-nB1-n.
9
10. Types of Combichem
Combinatorial chemistry is of two types:
SOLID PHASE COMBINATORIAL CHEMISTRY
(Compound library synthesized on solid phase such as resin bead)
SOLUTION PHASE COMBINATORIAL CHEMISTRY
(Compound library synthesized in solvent in the reaction flask)
10
11. Solid phase Combichem
STEPS:
Attach the starting molecule to an inert solid/resin bead.
Addition of excess of reagents to the solution.
Separation of products (attached to resin beads) by simple filteration.
Cleavage & isolation of products from the beads.
REQUIREMENTS:
Solid support (Resin beads)
An anchor or linker.
A bond linking the substrate to the linker.
A means of cleaving the product from the linker at the end.
Protecting groups
11
12. Solid phase Combichem
EXAMPLES OF SOLID SUPPORTS:
Partially cross-linked polystyrene beads: Polystyrene is cross linked
with divinyl benzene, hydrophobic in nature, causes problems in peptide
synthesis due to peptide folding.
Sheppard’s polyamide resin - more polar.
Tentagel resin - similar environment to ether
Beads, pins and functionalised glass surfaces
CHARACTERISTICS OF SOLID SUPPORT:
Beads must be able to swell in the solvent used, and remain stable.
Most reactions occur in the bead interior.
12
Resin bead Swelling
Linkers
Starting material,
reagents and solvent
13. Solid phase Combichem
ANCHOR OR LINKER:
A molecular moiety which is covalently attached to the solid support,
and which contains a reactive functional group.
Allows attachment of the first reactant.
The link must be stable to the reaction conditions in the synthesis but
easily cleaved to release the final compound.
Different linkers are available depending on the functional group to be
attached and the desired functional group on the product.
Resins are named to define the linker e.g.
Merrifield resin
Wang resin
Rink amide resin
Photolabile anchors
Traceless anchors
13
14. Solid phase Combichem
PROTECTING GROUPS:
A protecting group is reversibly attached to the functional group to
convert it to a less reactive form.
When the protection is no longer needed, the protecting group is cleaved
and the original functionality is restored.
protecting group to be stable under the expected reaction conditions and
to be cleavable - if possible-at mild reaction conditions.
Some of the protecting groups most widely used in peptide synthesis
are:
Benzyl carbonyl (Z) group
t-butoxy carbonyl (Boc) group
9-fluorenyl methoxy carbonyl (Fmoc) group
14
15. Solid phase Combichem
ADVANTAGES OF SOLID PHASE SYNTHESIS:
Specific reactants can be bound to specific beads.
Beads can be mixed and reacted in the same reaction vessel.
Products formed are distinctive for each bead and physically
distinct.
Excess reagents can be used to drive reactions to completion.
Excess reagents and by products are easily removed.
Reaction intermediates are attached to bead and do not need to be
isolated and purified.
Individual beads can be separated to isolate individual products.
Polymeric support can be regenerated and reused after cleaving
the product.
Automation is possible
15
16. Solid phase Combichem
DISADVANTAGES OF SOLID PHASE SYNTHESIS:
Not all syntheses can be done solid phase.
Some molecules don’t attach well to beads
Some chemistry just doesn’t work in this fashion
Removal of product from bead, can be damaging to product if not
careful
Typically, kinetics not the same.
Reaction rates can be slower
Difficult to monitor the progress of reaction when the substrate and
product are attached to the solid phase.
Assessment of the purity of the resin attached intermediates is also
difficult.
Purifying the final product after cleavage from the resin also proves to
be a challenge.
16
17. Solution phase Combichem
All chemical reactions are conducted simultaneously, preferably in well-
ordered sets (arrays) of reaction vessels in solution.
Soluble polymer are used as support for the product.
Limitation
when numbers of reagents are taken together in a solution
it can result in several side reactions and
Lead to polymerization giving a tarry mass.
Rectification
A new approach is developed in which all chemical structure
combinations are prepared separately, in parallel on a giving building
block using an automated robotic apparatus.
17
18. Combinatorial techniques
There are mainly two combinatorial techniques:
SPLIT & MIX SYNTHESIS/PORTIONING-MIXING SYNTHESIS
(One bead-one compound library)
PARALLEL SYNTHESIS
(One vessel-one Compound library)
18
19. Split and mix synthesis
Good to generate large libraries.
Resin beads are split into
different vessels.
Then reacted, shuffled, and
split again.
1000 compund library prepared
from 10 building blocks in each
step 30 reaction steps.
19
20. Split and mix synthesis
ADVANTAGES OF SPLIT & MIX SYNTHESIS:
Only few reaction vessels are required.
Large libraries (up to 105 compounds) can be quickly generated.
DISADVANTAGES OF SPLIT & MIX SYNTHESIS:
Large amount of resin beads are required.
The amount of synthesized product is small.
Complex mixtures are formed.
Deconvolution or tagging required.
20
21. Parallel synthesis
Each compound is synthesized
in specific reaction vessel.
Each starting material is
reacted with each building
block separately.
Then product is split into
portions, reacted with different
buildind block separately again.
21
22. Parallel synthesis
ADVANTAGES OF PARALLEL SYNTHESIS:
It creates compounds individually & in its own vessels.
Identity of products are already known.
Each compound is substantially pure in its location.
DISADVANTAGES OF PARALLEL SYNTHESIS:
Applicable only for medium libraries.
Large amount of vessels required.
Large number of reactions to be performed.
22
23. Screening methods
Screening is the process of determining whether compounds in a
chemical library have a desired chemical or biological activity, without
necessarily identifying the precise chemical nature of the compound(s)
being screened.
METHODS OF SCREENING OF COMBICHEM LIBRARIES:
Test mixture in solution
Test individual compounds in solution
Test compounds on the bead
23
24. Encoding methods
The process of identification of active compound in a mixture of
compounds is known as Encoding.
METHODS OF ENCODING OF COMBICHEM LIBRARIES:
Positional encoding (iterative resynthesis and rescreening)
Chemical encoding (Tagging)
Electronic encoding
24