SlideShare a Scribd company logo
ENZYME INHIBITION
Content
• Enzyme
• Kinetics of Enzymes
• Enzyme inhibition
• Classification of Enzyme inhibitors
• Enzyme inhibitors in medicine
• Enzyme inhibitors in basic research
• Rational design of non-covalently binding enzyme
inhibitors
• Rational design of covalently binding enzyme
inhibitors
Enzymes
 Enzymes are soluble, colloidal, organic catalysts, formed by
living cells specific in action, protein in nature, inactive at zero
degree celcius and destroyed by moist heat at 100 degree
celcius.
 Description :
Enzymes are the specialised proteins which catalyze various
biochemical reactions.
The concept of enzyme inhibition is routinely utilized to affect
biosynthesis and metabolic pattern of various hormones,
autocoids, and neurotransmitters.
In 1926, J.B. Sumner have isolated urease.
Each enzyme is assigned with
1. Recommended name
2. Systemic name
3. Classification number.
How enzyme catalyse reaction?
Enzymes provide a reaction surface and a suitable environment.
 Enzymes bring reactants together and position them correctly so
that they easily attain their transitionstate confi gurations.
 Enzymes weaken bonds in the reactants.
 Enzymes may participate in the reaction mechanism.
 Enzymes form stronger interactions with the transition state than
with the substrate or the product.
Enzyme Kinetics
• Enzyme kinetics is the study of the chemical
reactions that are catalysed by enzymes.
• In enzyme kinetics, the reaction rate is
measured and the effects of varying the
conditions of the reaction is investigated.
Michaelis–Menten Equation
• It explain how an enzyme can cause kinetic rate
enhancement of a reaction and why the rate of a
reaction depends on the concentration of enzyme
present.
• where KM is called the Michaelis Constant.
• KM is the substrate concentration required to reach half-
maximal velocity (vmax/2).
• KM is a measure of a substrate’s affinity for the enzyme.
• Considering the total enzyme concentration the maximal
rate, that the enzyme can attain is Vmax.
• Vmax is equal to the product of the catalytic rate
constant (kcat) and the concentration of the enzyme.
ENZYME
ACTIVITY
pH
TEMPERATURE
ENZYME
CONCENTRATION
TIME
PRODUCT
CONCENTRATION
EFFECT OF
RADIATION
Classification of enzyme inhibitors
• The inhibition of a suitably selected target enzyme leads
to build up in concentration of substrates and a
corrosponding decrease in the concentration of the
metabolites.
• Important parameters for selecting an enzyme inhibitor
are:
1.Biochemical environment of the target enzyme,
2.Specificity of action,
3.The time period for which an enzyme is blocked.
Reversible Inhibition
• Inhibitor binds to Enzyme reversibly through weak non-
covelent interactions.
• An Equilibrium is established between the free inhibitor
and EI Complex and is defined by an equilibrium constant
(Ki)
• Reversible Inhibitors depending on concentration of E, S
and I, show a definite degree of inhibition which is
reached fairly rapidly and remains constant when initial
velocity studies are carried out.
E I EI
The reversible inhibition is further sub-divided into:
I. Competitive inhibition
II. Non-competitive inhibition
I. Competitive inhibition : The inhibitor which closely resembles
the real substrate (S) is regarded as a substrate analogue.
• The inhibitor competes with substrate and binds at the active site
of the enzyme but does not undergo any catalysis.
• As long as the competitive inhibitor holds the active site, the
enzyme is not available for the substrate to bind. During the
reaction, ES and EI complexes are formed .
• The relative concentration of the substrate and inhibitor and their
respective affinity with the enzyme determines the degree of
competitive inhibition.
• The inhibition could be overcome by a high substrate
concentration. In competitive inhibition, the Km value increases
whereas Vmax remains unchanged .
The inhibitors action is proportional to its concentration
Example for Competitive Inhibition
Competitive inhibition accounts for the antibacterial action of
sulfanilamide which is a structural analog of PABA
Sulfanilamide inhibits the bacterial enzyme dihydropteroate
synthetase which catalyzes the incorporation of PABA into 7,8-
dihydropteroic acid.
NH2
SO2NH2COOH
NH2
II.Non-competitive inhibition :
• The inhibitor binds at a site other than the active site on the
enzyme surface. This binding impairs the enzyme function. The
inhibitor has no structural resemblance with the substrate.
• However, there usually exists a strong affinity for the inhibitor to
bind at the second site. In fact, the inhibitor does not interfere with
the enzyme-substrate binding. But the catalysis is prevented,
possibly due to a distortion in the enzyme conformation.
• The inhibitor generally binds with the enzyme as well as the ES
complex.
• For non-competitive inhibition, the Km value is unchanged while
Vmax is lowered .
• Heavy metal ions (Ag+, Pb2+, Hg2+ etc.) can non-competitively
inhibit the enzymes by binding with cysteinyl sulfhydryl groups.
Irreversible Inhibition
o Inhibitor binds at or near the active site of the enzyme
irreversibly, usually by covalent bonds, so it can’t dissociate
from the enzyme
o No equilibrium exits
o Effectiveness of I is expressed not by equilibrium constant but
by a velocity constant, which determines the fraction of the
enzyme inhibited in a given period of time by a certain
concentration of the I.
E I EI
Suicide inhibition:-
• Suicide inhibition is a specialized form of irreversible inhibition. In this
case, the original inhibitor (the structural analogue/competitive
inhibitor) is converted to a more potent form by the same enzyme
that ought to be inhibited.
• The so formed inhibitor binds irreversibly with the enzyme. This is in
contrast to the original inhibitor which binds reversibly.
• A good example of suicide inhibition is allopurinol an inhibitor of
xanthine oxidase, gets converted to alloxanthine, a more effective
inhibitor of this enzyme.
• The use of certain purine and pyrimidine analogues in cancer therapy
is also explained on the basis suicide inhibition. For instance, 5-
fluorouracil gets converted to fluorodeoxyuridylate which inhibits
the enzyme thymidylate synthase, and thus nucleotide synthesis
3. Allosteric inhibition
The details of this type of inhibition are given under allosteric
regulation as a part of the regulation of enzyme activity in the living
system.
Enzyme inhibition by drugs
Enzymes are the natural targets for development of pharmacologic
agents. Many of the drugs used in the treatment of diseases act as
enzyme inhibitors.
l Cholesterol loweing statin drugs (lovastatin) inhibit the enzyme HMG
CoA reductase.
Drugs (tenofovir, emtricitabine) employed to
block HIV replication inhibit the enzyme viral reverse transcriptase.
Hypertension is often treated by the drugs (captopril, enalapril )which
inhibit angiotensin converting enzyme.
Enzyme inhibitors in medicine
• A selective inhibitor may block either a single enzyme or a
group of enzymes.
• This will results in either a decrease in the concentration of
enzymatic products or an increase in the concentration of
enzymatic substrates.
• The effectiveness of an enzyme inhibitor as a therapeutic
agent will depend on :
a. The potency of the inhibitor
b. Its specificity
c. The choice of a metabolic pathway
d. The inhibitor or derivative possessing appropriate
pharmacokinetic characteristics
• Low dosage and high specificity combine to reduce the
toxicity problems.
• High specificity can avoid depletion of the inhibitor
concentrations in the host by non-specific pathways.
• Enzyme inhibitors used in treatment of bacterial,
fungal, viral and parasite diseases:
Enzyme inhibitors used in treatment of bacterial,
fungal, viral and parasite diseases:
Enzyme inhibitors used in various
human disease states
Enzyme inhibitors used in treatment of
cancer
Enzyme inhibitors in basic research
• Enzyme inhibitors have found a multitude of uses:
1. As useful tools for the elucidation of structure and
function of enzymes.
2. As probes for chemical and kinetic processes and in
the detection of short-lived reaction intermediates.
3. Product inhibition patterns provide information about
an enzymes kinetic mechanism and the order of
substrate binding.
4. Covalently binding enzyme inhibitors have
been used to identify active-site amino acid
residues.
5. Reversible enzyme inhibitors are used to
facilitate enzyme purification.
6. Immobilized enzyme inhibitors can also be
used to identify their intracellular targets
whereas irreversible inhibitors can be used to
localize and quantify enzymes in-vivo.
Rational design of non-covalently
binding enzyme inhibitors
• This class of inhibitors binds to the enzyme's active
site without forming a covalent bond.
• Therefore the affinity and specificity of the inhibitor
for the active site will depend on a combination of
the electrostatic and dispersive forces, and
hydrophobic and hydrogen-bonding interactions.
• To understand the design concepts of the various
types of non-covalently binding enzyme inhibitors, a
basic knowledge of the binding forces between an
enzyme's active site and its inhibitors is required.
Forces involved
in an inhibitor /
substrate
binding
Ionic
(electrostatic)
interactions
Hydrogen
bonding
Ion dipole and
dipole-dipole
interactions
Hydrophobic
interactions
Van der Waals
interactions
Rational design of covalently binding
enzyme inhibitors
• The targets for these inhibitors are the chemically
reactive groups found within the enzyme's active site.
These groups, in the majority of cases, are
nucleophiles.
• In some cases the -NH, and -COOH groups of the
enzyme's N- and C-termini, respectively, are also active
site nucleophiles, whereas enzymic cofactors may also
provide targets for covalently binding inhibitors.
• Arginine is the only common amino acid that has an
electrophilic side chain and it also can be modified with
suitable nucleophilic agents.
Targets for
covalently binding
enzyme inhibitors
Nucleophiles such as –OH
group of
serine,threonine, tyrosine
-SH group of cysteine
-COOH groups of aspartic
and glutamic acid residues
imidazole ring of histidine
£-amino group of lysine
ENZYME INHIBITION MORE INTERESTING IN CHEMISTRY WAY

More Related Content

What's hot

Role of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentRole of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentKaranvir Rajput
 
Artificial enzymes presentation.pptx
Artificial enzymes presentation.pptxArtificial enzymes presentation.pptx
Artificial enzymes presentation.pptxFirujAhmed2
 
Biological Drug Targets.pptx
Biological Drug Targets.pptxBiological Drug Targets.pptx
Biological Drug Targets.pptxVarshaJindaniya
 
Natural products as leads for new pharmaceuticals
Natural products as leads  for new pharmaceuticalsNatural products as leads  for new pharmaceuticals
Natural products as leads for new pharmaceuticalsShikha Popali
 
01.Rational Design of Enzyme inhibition.pptx
01.Rational Design of Enzyme inhibition.pptx01.Rational Design of Enzyme inhibition.pptx
01.Rational Design of Enzyme inhibition.pptxPurushothamKN1
 
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
 
Chemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of prostaglandins, leukotrienes and thromboxanesChemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of prostaglandins, leukotrienes and thromboxanesAbhimanyu Awasthi
 
STEREOCHEMISTRY AND DRUG ACTION.pptx
STEREOCHEMISTRY AND DRUG ACTION.pptxSTEREOCHEMISTRY AND DRUG ACTION.pptx
STEREOCHEMISTRY AND DRUG ACTION.pptxAchalYawalkar
 
Synthetic Reagent and Its Applications (M. Pharm)
Synthetic Reagent and Its Applications (M. Pharm)Synthetic Reagent and Its Applications (M. Pharm)
Synthetic Reagent and Its Applications (M. Pharm)MohdShafeeque4
 
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]Shikha Popali
 
Skv Enzyme Kinetics and Principles of Enzyme Inhibition
Skv Enzyme Kinetics and Principles of Enzyme InhibitionSkv Enzyme Kinetics and Principles of Enzyme Inhibition
Skv Enzyme Kinetics and Principles of Enzyme InhibitionSACHINKUMARVISHWAKAR4
 
Heterocyclic Organic Reaction - By Vishal Dakhale
Heterocyclic Organic Reaction - By Vishal DakhaleHeterocyclic Organic Reaction - By Vishal Dakhale
Heterocyclic Organic Reaction - By Vishal DakhaleVishalDakhale
 

What's hot (20)

Role of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentRole of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agent
 
Artificial enzymes presentation.pptx
Artificial enzymes presentation.pptxArtificial enzymes presentation.pptx
Artificial enzymes presentation.pptx
 
Biological Drug Targets.pptx
Biological Drug Targets.pptxBiological Drug Targets.pptx
Biological Drug Targets.pptx
 
Natural products as leads for new pharmaceuticals
Natural products as leads  for new pharmaceuticalsNatural products as leads  for new pharmaceuticals
Natural products as leads for new pharmaceuticals
 
Peptidomimetics
PeptidomimeticsPeptidomimetics
Peptidomimetics
 
01.Rational Design of Enzyme inhibition.pptx
01.Rational Design of Enzyme inhibition.pptx01.Rational Design of Enzyme inhibition.pptx
01.Rational Design of Enzyme inhibition.pptx
 
Traube purine synthesis
Traube purine synthesisTraube purine synthesis
Traube purine synthesis
 
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]
 
Chemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of prostaglandins, leukotrienes and thromboxanesChemistry of prostaglandins, leukotrienes and thromboxanes
Chemistry of prostaglandins, leukotrienes and thromboxanes
 
Protecting groups
Protecting groupsProtecting groups
Protecting groups
 
STEREOCHEMISTRY AND DRUG ACTION.pptx
STEREOCHEMISTRY AND DRUG ACTION.pptxSTEREOCHEMISTRY AND DRUG ACTION.pptx
STEREOCHEMISTRY AND DRUG ACTION.pptx
 
AMC PPT 4.pptx
AMC PPT 4.pptxAMC PPT 4.pptx
AMC PPT 4.pptx
 
Synthetic Reagent and Its Applications (M. Pharm)
Synthetic Reagent and Its Applications (M. Pharm)Synthetic Reagent and Its Applications (M. Pharm)
Synthetic Reagent and Its Applications (M. Pharm)
 
Terpenoids
Terpenoids Terpenoids
Terpenoids
 
peptidomimetics.pdf
peptidomimetics.pdfpeptidomimetics.pdf
peptidomimetics.pdf
 
synthon approach
 synthon approach  synthon approach
synthon approach
 
Peptidomimitics
PeptidomimiticsPeptidomimitics
Peptidomimitics
 
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
 
Skv Enzyme Kinetics and Principles of Enzyme Inhibition
Skv Enzyme Kinetics and Principles of Enzyme InhibitionSkv Enzyme Kinetics and Principles of Enzyme Inhibition
Skv Enzyme Kinetics and Principles of Enzyme Inhibition
 
Heterocyclic Organic Reaction - By Vishal Dakhale
Heterocyclic Organic Reaction - By Vishal DakhaleHeterocyclic Organic Reaction - By Vishal Dakhale
Heterocyclic Organic Reaction - By Vishal Dakhale
 

Similar to ENZYME INHIBITION MORE INTERESTING IN CHEMISTRY WAY

Enzyme inhibitors as therapeutic tools (with 2 case study)
Enzyme inhibitors as therapeutic tools (with 2 case study)Enzyme inhibitors as therapeutic tools (with 2 case study)
Enzyme inhibitors as therapeutic tools (with 2 case study)Tosim Mulani
 
ENZYMES 2023.pptx
ENZYMES 2023.pptxENZYMES 2023.pptx
ENZYMES 2023.pptxAyman Hany
 
Basics of Enzyme Catalysis
Basics of Enzyme CatalysisBasics of Enzyme Catalysis
Basics of Enzyme CatalysisFahad Ullah
 
Enzymes and enzymes inhibition, GPCR
Enzymes and enzymes inhibition, GPCREnzymes and enzymes inhibition, GPCR
Enzymes and enzymes inhibition, GPCRAbhishekJoshi312
 
Presentation (2) (1)
Presentation (2) (1)Presentation (2) (1)
Presentation (2) (1)ZeenatJahan10
 
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY Enzyme
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY EnzymeD. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY Enzyme
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY EnzymeArun Kumar
 
Clinical Enzymology.pdf
Clinical Enzymology.pdfClinical Enzymology.pdf
Clinical Enzymology.pdfqahtanali2
 
factors Affecting Enzyme activity
factors  Affecting   Enzyme  activityfactors  Affecting   Enzyme  activity
factors Affecting Enzyme activityShamim Akram
 
Enzyme inhibitors, reversible_and_irreversible
Enzyme inhibitors, reversible_and_irreversibleEnzyme inhibitors, reversible_and_irreversible
Enzyme inhibitors, reversible_and_irreversibleansari nazeef
 
Biochemistry lecture notes enzymes
Biochemistry lecture notes enzymesBiochemistry lecture notes enzymes
Biochemistry lecture notes enzymesRengesh Balakrishnan
 
Enzyme inhibition ppt final
Enzyme inhibition ppt finalEnzyme inhibition ppt final
Enzyme inhibition ppt finalSwapnil Agarwal
 

Similar to ENZYME INHIBITION MORE INTERESTING IN CHEMISTRY WAY (20)

Enzymes
EnzymesEnzymes
Enzymes
 
Enzyme inhibitors as therapeutic tools (with 2 case study)
Enzyme inhibitors as therapeutic tools (with 2 case study)Enzyme inhibitors as therapeutic tools (with 2 case study)
Enzyme inhibitors as therapeutic tools (with 2 case study)
 
Enzymes 2019
Enzymes 2019Enzymes 2019
Enzymes 2019
 
ENZYMES 2023.pptx
ENZYMES 2023.pptxENZYMES 2023.pptx
ENZYMES 2023.pptx
 
Enzyme
EnzymeEnzyme
Enzyme
 
Basics of Enzyme Catalysis
Basics of Enzyme CatalysisBasics of Enzyme Catalysis
Basics of Enzyme Catalysis
 
Regulation of enzyme activity
Regulation of enzyme activityRegulation of enzyme activity
Regulation of enzyme activity
 
Targets of drug action: Enzymes
Targets of drug action: EnzymesTargets of drug action: Enzymes
Targets of drug action: Enzymes
 
Enzymes and enzymes inhibition, GPCR
Enzymes and enzymes inhibition, GPCREnzymes and enzymes inhibition, GPCR
Enzymes and enzymes inhibition, GPCR
 
Presentation (2) (1)
Presentation (2) (1)Presentation (2) (1)
Presentation (2) (1)
 
Enzyme
EnzymeEnzyme
Enzyme
 
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY Enzyme
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY EnzymeD. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY Enzyme
D. Pharm BIOCHEMISTRY AND CLINICAL PATHOLOGY Enzyme
 
Clinical Enzymology.pdf
Clinical Enzymology.pdfClinical Enzymology.pdf
Clinical Enzymology.pdf
 
factors Affecting Enzyme activity
factors  Affecting   Enzyme  activityfactors  Affecting   Enzyme  activity
factors Affecting Enzyme activity
 
Enzyme inhibitors, reversible_and_irreversible
Enzyme inhibitors, reversible_and_irreversibleEnzyme inhibitors, reversible_and_irreversible
Enzyme inhibitors, reversible_and_irreversible
 
Enzymes
EnzymesEnzymes
Enzymes
 
Enzymes.pptx
Enzymes.pptxEnzymes.pptx
Enzymes.pptx
 
Enzyme
Enzyme Enzyme
Enzyme
 
Biochemistry lecture notes enzymes
Biochemistry lecture notes enzymesBiochemistry lecture notes enzymes
Biochemistry lecture notes enzymes
 
Enzyme inhibition ppt final
Enzyme inhibition ppt finalEnzyme inhibition ppt final
Enzyme inhibition ppt final
 

More from Shikha Popali

Steric parameters taft’s steric factor (es)
Steric parameters  taft’s steric factor (es)Steric parameters  taft’s steric factor (es)
Steric parameters taft’s steric factor (es)Shikha Popali
 
Stereochemistry in drug design
Stereochemistry in drug designStereochemistry in drug design
Stereochemistry in drug designShikha Popali
 
Bioanalytical method validation
Bioanalytical method validationBioanalytical method validation
Bioanalytical method validationShikha Popali
 
Antihypertensive drugs
Antihypertensive drugsAntihypertensive drugs
Antihypertensive drugsShikha Popali
 
Herbal ingredient hair and skin care
Herbal ingredient hair and skin careHerbal ingredient hair and skin care
Herbal ingredient hair and skin careShikha Popali
 
problem assso with oral cavity
problem assso with oral cavityproblem assso with oral cavity
problem assso with oral cavityShikha Popali
 
problems associated with skin[ as per Pharmaceutics]
problems associated with skin[ as per Pharmaceutics]problems associated with skin[ as per Pharmaceutics]
problems associated with skin[ as per Pharmaceutics]Shikha Popali
 
cosmetics and cosmeticals [department of pharmaceutics]
cosmetics and cosmeticals [department of pharmaceutics]cosmetics and cosmeticals [department of pharmaceutics]
cosmetics and cosmeticals [department of pharmaceutics]Shikha Popali
 
MUTUAL PRODRUG [PHARMACEUTICALS]
MUTUAL PRODRUG [PHARMACEUTICALS]MUTUAL PRODRUG [PHARMACEUTICALS]
MUTUAL PRODRUG [PHARMACEUTICALS]Shikha Popali
 
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]Shikha Popali
 
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]Shikha Popali
 
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]Shikha Popali
 
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDE
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDESynthetic reagent and applications OF ALUMINIUM ISOPROPOXIDE
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDEShikha Popali
 
PHASE TRANSFER CATALYSIS [PTC]
PHASE TRANSFER CATALYSIS [PTC] PHASE TRANSFER CATALYSIS [PTC]
PHASE TRANSFER CATALYSIS [PTC] Shikha Popali
 
SWERTIA CHIRATA NATURAL PRODUCT OF PHARMACEUTICALS
SWERTIA CHIRATA  NATURAL PRODUCT OF PHARMACEUTICALSSWERTIA CHIRATA  NATURAL PRODUCT OF PHARMACEUTICALS
SWERTIA CHIRATA NATURAL PRODUCT OF PHARMACEUTICALSShikha Popali
 
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]Shikha Popali
 
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)Shikha Popali
 
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]Shikha Popali
 
Dicyclohexylcarbodiimide [DCC]
Dicyclohexylcarbodiimide [DCC]Dicyclohexylcarbodiimide [DCC]
Dicyclohexylcarbodiimide [DCC]Shikha Popali
 
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDSCOMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDSShikha Popali
 

More from Shikha Popali (20)

Steric parameters taft’s steric factor (es)
Steric parameters  taft’s steric factor (es)Steric parameters  taft’s steric factor (es)
Steric parameters taft’s steric factor (es)
 
Stereochemistry in drug design
Stereochemistry in drug designStereochemistry in drug design
Stereochemistry in drug design
 
Bioanalytical method validation
Bioanalytical method validationBioanalytical method validation
Bioanalytical method validation
 
Antihypertensive drugs
Antihypertensive drugsAntihypertensive drugs
Antihypertensive drugs
 
Herbal ingredient hair and skin care
Herbal ingredient hair and skin careHerbal ingredient hair and skin care
Herbal ingredient hair and skin care
 
problem assso with oral cavity
problem assso with oral cavityproblem assso with oral cavity
problem assso with oral cavity
 
problems associated with skin[ as per Pharmaceutics]
problems associated with skin[ as per Pharmaceutics]problems associated with skin[ as per Pharmaceutics]
problems associated with skin[ as per Pharmaceutics]
 
cosmetics and cosmeticals [department of pharmaceutics]
cosmetics and cosmeticals [department of pharmaceutics]cosmetics and cosmeticals [department of pharmaceutics]
cosmetics and cosmeticals [department of pharmaceutics]
 
MUTUAL PRODRUG [PHARMACEUTICALS]
MUTUAL PRODRUG [PHARMACEUTICALS]MUTUAL PRODRUG [PHARMACEUTICALS]
MUTUAL PRODRUG [PHARMACEUTICALS]
 
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]
TITANIUM CHLORIDE [PHARMACEUTICAL REAGENT]
 
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]
OLIGONUCLEOTIDE THERAPY [ TECHNIQUES, APPLICATIONS]
 
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]
 
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDE
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDESynthetic reagent and applications OF ALUMINIUM ISOPROPOXIDE
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDE
 
PHASE TRANSFER CATALYSIS [PTC]
PHASE TRANSFER CATALYSIS [PTC] PHASE TRANSFER CATALYSIS [PTC]
PHASE TRANSFER CATALYSIS [PTC]
 
SWERTIA CHIRATA NATURAL PRODUCT OF PHARMACEUTICALS
SWERTIA CHIRATA  NATURAL PRODUCT OF PHARMACEUTICALSSWERTIA CHIRATA  NATURAL PRODUCT OF PHARMACEUTICALS
SWERTIA CHIRATA NATURAL PRODUCT OF PHARMACEUTICALS
 
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]
LIQUID CHROMATOGRAPHY- MASS SPECTROSCOPY[LC-MS]
 
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)
EVAPORATION (LIQUID CONVERSION INTO VAPOUR PRESSURE)
 
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]
Homogeneous catalysis [ MPHARM, MSC, BPHARM, BSC]
 
Dicyclohexylcarbodiimide [DCC]
Dicyclohexylcarbodiimide [DCC]Dicyclohexylcarbodiimide [DCC]
Dicyclohexylcarbodiimide [DCC]
 
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDSCOMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDS
 

Recently uploaded

size separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceuticssize separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceuticspragatimahajan3
 
Basic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & EngineeringBasic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & EngineeringDenish Jangid
 
The Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. HenryThe Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. HenryEugene Lysak
 
Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17Celine George
 
Neurulation and the formation of the neural tube
Neurulation and the formation of the neural tubeNeurulation and the formation of the neural tube
Neurulation and the formation of the neural tubeSaadHumayun7
 
Basic phrases for greeting and assisting costumers
Basic phrases for greeting and assisting costumersBasic phrases for greeting and assisting costumers
Basic phrases for greeting and assisting costumersPedroFerreira53928
 
PART A. Introduction to Costumer Service
PART A. Introduction to Costumer ServicePART A. Introduction to Costumer Service
PART A. Introduction to Costumer ServicePedroFerreira53928
 
Industrial Training Report- AKTU Industrial Training Report
Industrial Training Report- AKTU Industrial Training ReportIndustrial Training Report- AKTU Industrial Training Report
Industrial Training Report- AKTU Industrial Training ReportAvinash Rai
 
Basic_QTL_Marker-assisted_Selection_Sourabh.ppt
Basic_QTL_Marker-assisted_Selection_Sourabh.pptBasic_QTL_Marker-assisted_Selection_Sourabh.ppt
Basic_QTL_Marker-assisted_Selection_Sourabh.pptSourabh Kumar
 
[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online Presentation[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online PresentationGDSCYCCE
 
How to Break the cycle of negative Thoughts
How to Break the cycle of negative ThoughtsHow to Break the cycle of negative Thoughts
How to Break the cycle of negative ThoughtsCol Mukteshwar Prasad
 
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...Nguyen Thanh Tu Collection
 
Application of Matrices in real life. Presentation on application of matrices
Application of Matrices in real life. Presentation on application of matricesApplication of Matrices in real life. Presentation on application of matrices
Application of Matrices in real life. Presentation on application of matricesRased Khan
 
Gyanartha SciBizTech Quiz slideshare.pptx
Gyanartha SciBizTech Quiz slideshare.pptxGyanartha SciBizTech Quiz slideshare.pptx
Gyanartha SciBizTech Quiz slideshare.pptxShibin Azad
 
How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17Celine George
 
slides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptxslides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptxCapitolTechU
 
Championnat de France de Tennis de table/
Championnat de France de Tennis de table/Championnat de France de Tennis de table/
Championnat de France de Tennis de table/siemaillard
 
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...Sayali Powar
 
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdfDanh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdfQucHHunhnh
 

Recently uploaded (20)

size separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceuticssize separation d pharm 1st year pharmaceutics
size separation d pharm 1st year pharmaceutics
 
Basic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & EngineeringBasic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
Basic Civil Engg Notes_Chapter-6_Environment Pollution & Engineering
 
The Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. HenryThe Last Leaf, a short story by O. Henry
The Last Leaf, a short story by O. Henry
 
Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17Features of Video Calls in the Discuss Module in Odoo 17
Features of Video Calls in the Discuss Module in Odoo 17
 
Neurulation and the formation of the neural tube
Neurulation and the formation of the neural tubeNeurulation and the formation of the neural tube
Neurulation and the formation of the neural tube
 
Operations Management - Book1.p - Dr. Abdulfatah A. Salem
Operations Management - Book1.p  - Dr. Abdulfatah A. SalemOperations Management - Book1.p  - Dr. Abdulfatah A. Salem
Operations Management - Book1.p - Dr. Abdulfatah A. Salem
 
Basic phrases for greeting and assisting costumers
Basic phrases for greeting and assisting costumersBasic phrases for greeting and assisting costumers
Basic phrases for greeting and assisting costumers
 
PART A. Introduction to Costumer Service
PART A. Introduction to Costumer ServicePART A. Introduction to Costumer Service
PART A. Introduction to Costumer Service
 
Industrial Training Report- AKTU Industrial Training Report
Industrial Training Report- AKTU Industrial Training ReportIndustrial Training Report- AKTU Industrial Training Report
Industrial Training Report- AKTU Industrial Training Report
 
Basic_QTL_Marker-assisted_Selection_Sourabh.ppt
Basic_QTL_Marker-assisted_Selection_Sourabh.pptBasic_QTL_Marker-assisted_Selection_Sourabh.ppt
Basic_QTL_Marker-assisted_Selection_Sourabh.ppt
 
[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online Presentation[GDSC YCCE] Build with AI Online Presentation
[GDSC YCCE] Build with AI Online Presentation
 
How to Break the cycle of negative Thoughts
How to Break the cycle of negative ThoughtsHow to Break the cycle of negative Thoughts
How to Break the cycle of negative Thoughts
 
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...
50 ĐỀ LUYỆN THI IOE LỚP 9 - NĂM HỌC 2022-2023 (CÓ LINK HÌNH, FILE AUDIO VÀ ĐÁ...
 
Application of Matrices in real life. Presentation on application of matrices
Application of Matrices in real life. Presentation on application of matricesApplication of Matrices in real life. Presentation on application of matrices
Application of Matrices in real life. Presentation on application of matrices
 
Gyanartha SciBizTech Quiz slideshare.pptx
Gyanartha SciBizTech Quiz slideshare.pptxGyanartha SciBizTech Quiz slideshare.pptx
Gyanartha SciBizTech Quiz slideshare.pptx
 
How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17How to Manage Notification Preferences in the Odoo 17
How to Manage Notification Preferences in the Odoo 17
 
slides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptxslides CapTechTalks Webinar May 2024 Alexander Perry.pptx
slides CapTechTalks Webinar May 2024 Alexander Perry.pptx
 
Championnat de France de Tennis de table/
Championnat de France de Tennis de table/Championnat de France de Tennis de table/
Championnat de France de Tennis de table/
 
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
UNIT – IV_PCI Complaints: Complaints and evaluation of complaints, Handling o...
 
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdfDanh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
Danh sách HSG Bộ môn cấp trường - Cấp THPT.pdf
 

ENZYME INHIBITION MORE INTERESTING IN CHEMISTRY WAY

  • 2. Content • Enzyme • Kinetics of Enzymes • Enzyme inhibition • Classification of Enzyme inhibitors • Enzyme inhibitors in medicine • Enzyme inhibitors in basic research • Rational design of non-covalently binding enzyme inhibitors • Rational design of covalently binding enzyme inhibitors
  • 3.
  • 4. Enzymes  Enzymes are soluble, colloidal, organic catalysts, formed by living cells specific in action, protein in nature, inactive at zero degree celcius and destroyed by moist heat at 100 degree celcius.  Description : Enzymes are the specialised proteins which catalyze various biochemical reactions. The concept of enzyme inhibition is routinely utilized to affect biosynthesis and metabolic pattern of various hormones, autocoids, and neurotransmitters. In 1926, J.B. Sumner have isolated urease.
  • 5. Each enzyme is assigned with 1. Recommended name 2. Systemic name 3. Classification number.
  • 6.
  • 7. How enzyme catalyse reaction? Enzymes provide a reaction surface and a suitable environment.  Enzymes bring reactants together and position them correctly so that they easily attain their transitionstate confi gurations.  Enzymes weaken bonds in the reactants.  Enzymes may participate in the reaction mechanism.  Enzymes form stronger interactions with the transition state than with the substrate or the product.
  • 8. Enzyme Kinetics • Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. • In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction is investigated.
  • 9. Michaelis–Menten Equation • It explain how an enzyme can cause kinetic rate enhancement of a reaction and why the rate of a reaction depends on the concentration of enzyme present. • where KM is called the Michaelis Constant.
  • 10. • KM is the substrate concentration required to reach half- maximal velocity (vmax/2). • KM is a measure of a substrate’s affinity for the enzyme. • Considering the total enzyme concentration the maximal rate, that the enzyme can attain is Vmax. • Vmax is equal to the product of the catalytic rate constant (kcat) and the concentration of the enzyme.
  • 12.
  • 13.
  • 14.
  • 15. Classification of enzyme inhibitors • The inhibition of a suitably selected target enzyme leads to build up in concentration of substrates and a corrosponding decrease in the concentration of the metabolites. • Important parameters for selecting an enzyme inhibitor are: 1.Biochemical environment of the target enzyme, 2.Specificity of action, 3.The time period for which an enzyme is blocked.
  • 16.
  • 17. Reversible Inhibition • Inhibitor binds to Enzyme reversibly through weak non- covelent interactions. • An Equilibrium is established between the free inhibitor and EI Complex and is defined by an equilibrium constant (Ki) • Reversible Inhibitors depending on concentration of E, S and I, show a definite degree of inhibition which is reached fairly rapidly and remains constant when initial velocity studies are carried out. E I EI
  • 18. The reversible inhibition is further sub-divided into: I. Competitive inhibition II. Non-competitive inhibition I. Competitive inhibition : The inhibitor which closely resembles the real substrate (S) is regarded as a substrate analogue. • The inhibitor competes with substrate and binds at the active site of the enzyme but does not undergo any catalysis. • As long as the competitive inhibitor holds the active site, the enzyme is not available for the substrate to bind. During the reaction, ES and EI complexes are formed . • The relative concentration of the substrate and inhibitor and their respective affinity with the enzyme determines the degree of competitive inhibition. • The inhibition could be overcome by a high substrate concentration. In competitive inhibition, the Km value increases whereas Vmax remains unchanged .
  • 19. The inhibitors action is proportional to its concentration
  • 20. Example for Competitive Inhibition Competitive inhibition accounts for the antibacterial action of sulfanilamide which is a structural analog of PABA Sulfanilamide inhibits the bacterial enzyme dihydropteroate synthetase which catalyzes the incorporation of PABA into 7,8- dihydropteroic acid. NH2 SO2NH2COOH NH2
  • 21. II.Non-competitive inhibition : • The inhibitor binds at a site other than the active site on the enzyme surface. This binding impairs the enzyme function. The inhibitor has no structural resemblance with the substrate. • However, there usually exists a strong affinity for the inhibitor to bind at the second site. In fact, the inhibitor does not interfere with the enzyme-substrate binding. But the catalysis is prevented, possibly due to a distortion in the enzyme conformation. • The inhibitor generally binds with the enzyme as well as the ES complex. • For non-competitive inhibition, the Km value is unchanged while Vmax is lowered . • Heavy metal ions (Ag+, Pb2+, Hg2+ etc.) can non-competitively inhibit the enzymes by binding with cysteinyl sulfhydryl groups.
  • 22.
  • 23. Irreversible Inhibition o Inhibitor binds at or near the active site of the enzyme irreversibly, usually by covalent bonds, so it can’t dissociate from the enzyme o No equilibrium exits o Effectiveness of I is expressed not by equilibrium constant but by a velocity constant, which determines the fraction of the enzyme inhibited in a given period of time by a certain concentration of the I. E I EI
  • 24. Suicide inhibition:- • Suicide inhibition is a specialized form of irreversible inhibition. In this case, the original inhibitor (the structural analogue/competitive inhibitor) is converted to a more potent form by the same enzyme that ought to be inhibited. • The so formed inhibitor binds irreversibly with the enzyme. This is in contrast to the original inhibitor which binds reversibly. • A good example of suicide inhibition is allopurinol an inhibitor of xanthine oxidase, gets converted to alloxanthine, a more effective inhibitor of this enzyme. • The use of certain purine and pyrimidine analogues in cancer therapy is also explained on the basis suicide inhibition. For instance, 5- fluorouracil gets converted to fluorodeoxyuridylate which inhibits the enzyme thymidylate synthase, and thus nucleotide synthesis
  • 25. 3. Allosteric inhibition The details of this type of inhibition are given under allosteric regulation as a part of the regulation of enzyme activity in the living system. Enzyme inhibition by drugs Enzymes are the natural targets for development of pharmacologic agents. Many of the drugs used in the treatment of diseases act as enzyme inhibitors. l Cholesterol loweing statin drugs (lovastatin) inhibit the enzyme HMG CoA reductase. Drugs (tenofovir, emtricitabine) employed to block HIV replication inhibit the enzyme viral reverse transcriptase. Hypertension is often treated by the drugs (captopril, enalapril )which inhibit angiotensin converting enzyme.
  • 26. Enzyme inhibitors in medicine • A selective inhibitor may block either a single enzyme or a group of enzymes. • This will results in either a decrease in the concentration of enzymatic products or an increase in the concentration of enzymatic substrates. • The effectiveness of an enzyme inhibitor as a therapeutic agent will depend on : a. The potency of the inhibitor b. Its specificity c. The choice of a metabolic pathway d. The inhibitor or derivative possessing appropriate pharmacokinetic characteristics
  • 27. • Low dosage and high specificity combine to reduce the toxicity problems. • High specificity can avoid depletion of the inhibitor concentrations in the host by non-specific pathways. • Enzyme inhibitors used in treatment of bacterial, fungal, viral and parasite diseases:
  • 28. Enzyme inhibitors used in treatment of bacterial, fungal, viral and parasite diseases:
  • 29. Enzyme inhibitors used in various human disease states
  • 30. Enzyme inhibitors used in treatment of cancer
  • 31. Enzyme inhibitors in basic research • Enzyme inhibitors have found a multitude of uses: 1. As useful tools for the elucidation of structure and function of enzymes. 2. As probes for chemical and kinetic processes and in the detection of short-lived reaction intermediates. 3. Product inhibition patterns provide information about an enzymes kinetic mechanism and the order of substrate binding.
  • 32. 4. Covalently binding enzyme inhibitors have been used to identify active-site amino acid residues. 5. Reversible enzyme inhibitors are used to facilitate enzyme purification. 6. Immobilized enzyme inhibitors can also be used to identify their intracellular targets whereas irreversible inhibitors can be used to localize and quantify enzymes in-vivo.
  • 33. Rational design of non-covalently binding enzyme inhibitors • This class of inhibitors binds to the enzyme's active site without forming a covalent bond. • Therefore the affinity and specificity of the inhibitor for the active site will depend on a combination of the electrostatic and dispersive forces, and hydrophobic and hydrogen-bonding interactions. • To understand the design concepts of the various types of non-covalently binding enzyme inhibitors, a basic knowledge of the binding forces between an enzyme's active site and its inhibitors is required.
  • 34. Forces involved in an inhibitor / substrate binding Ionic (electrostatic) interactions Hydrogen bonding Ion dipole and dipole-dipole interactions Hydrophobic interactions Van der Waals interactions
  • 35. Rational design of covalently binding enzyme inhibitors • The targets for these inhibitors are the chemically reactive groups found within the enzyme's active site. These groups, in the majority of cases, are nucleophiles. • In some cases the -NH, and -COOH groups of the enzyme's N- and C-termini, respectively, are also active site nucleophiles, whereas enzymic cofactors may also provide targets for covalently binding inhibitors. • Arginine is the only common amino acid that has an electrophilic side chain and it also can be modified with suitable nucleophilic agents.
  • 36. Targets for covalently binding enzyme inhibitors Nucleophiles such as –OH group of serine,threonine, tyrosine -SH group of cysteine -COOH groups of aspartic and glutamic acid residues imidazole ring of histidine £-amino group of lysine