Rational design of enzyme inhibitors( 2).pptx

Rational design of enzyme inhibitors

1. Rational design of enzyme inhibitors… Presented by , SUVAIV - 1600100395 Faculty of pharmacy ,integral university Lucknow .

2. Rational design of non covalently binding enzyme inhibitors… As their name indicates, 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. Traditionally, noncovalently binding enzyme inhibitors were analogs of substrates, products, or reaction intermediates .

3. Forces Involved in Forming the Enzyme- Inhibitor Complex Ionic (electrostatic) interactions, - 5 to 10 kcal Ion-dipole- 1 to 7 kcal dipole-dipole interactions – 1 to 7 kcal Hydrogen bonding- 1 to 7 kcal hydrophobic interactions – 1 kcal and Van der Waals interactions- 0.5 to 1 kcal

4. Classification of Noncovalent Inhibitors Based on their kinetics (1) rapid reversible, (2)Tight-binding,(3) Slow-binding, (4)Slow-tight-binding,(5) Irreversible, and(6) Pseudoirreversible inhibitors. Conversely, inhibitors classified on the basis of structure, such as (1)ground-state analogs, (2) multisubstrate inhibitors, and (3) transition-state analogs,

5. Rapid reversible Inhibitors ….. Competitive Non- competitive and Uncompetitive inhibitors Competitive Inhibitors. A competitive inhibitor often has structural features similar to those of the substrates whose reactions they inhibit. This means that a competitive inhibitor and enzyme's substrate are in direct competition for the same binding site on the enzyme. Consequently, binding of the substrate and the inhibitor are mutually exclusive.

6. Uncompetitive Inhibitors. Uncompetitive inhibitors do not bind to the free enzyme. They bind only to the enzyme-substrate complex to yield an inactive E S I complex

7. Examples of Rapid Reversible Inhibitors… One of the first reactions inhibited by a substrate analog was that catalyzed by succinate dehydrogenase . .

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