1 / 19

Lecture 7-Enzyme Inhibition-Drug Discovery

Lecture 7-Enzyme Inhibition-Drug Discovery. Aspirin (anti-inflammatory) Penicillin (effective agaist gram posiytive) Sulfonamides (anti-diarrhea) Anti HIV drugs. Competitive Inhibitors compete with the substrate for the active site

naava
Download Presentation

Lecture 7-Enzyme Inhibition-Drug Discovery

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lecture 7-Enzyme Inhibition-Drug Discovery • Aspirin (anti-inflammatory) • Penicillin (effective agaist gram posiytive) • Sulfonamides (anti-diarrhea) • Anti HIV drugs

  2. Competitive Inhibitors compete with the substrate for the active site • Non-Competitive inhibitors bind near but not at the active site • Irreversible inhibitors bind at the active site of the enzyme and form a covalent bond with a group at this site ENZYME INHIBITORS AS DRUGS

  3. Enzyme inhibition

  4. COMPETITIVE INHIBITORS E + S ES E + P + I EI Ki= [E][I]/[EI] V= Vmax S Km[1+(I/Ki)] +S

  5. Kinetics of competitive inhibitor binding Increase [S] to overcome inhibition Vmax attainable, Apparent Km is increased Ki = dissociation constant for inhibitor

  6. Vmax unaltered,Km increased Double reciprocal plot in the presence of a competitive inhibitor

  7. Methotrexate in cancer chemotherapy

  8. COMPETITIVE INHIBITORS AS DRUGS Thioadenine Adenine

  9. More competitive inhibitors as drugs • Doxycycline • competitive inhibitor of collagenase- control of periodontal disease • AZT-competitive inhibitor of HIV RT • Mozenavir and Tipranavir competitive inhibitors of HIV protease • Allopurinol (used in gout)—Oxypurinol—inhibits xanthine oxidase

  10. ENZYME INHIBITORS IN CLINICAL USE • A clinical application in Periodontitis

  11. NONCOMPETITIVE INHIBITION E + S ES E + P + + I I EI + S ESI Vmax S V= [1+(I/Ki)] Km + S

  12. Kinetics of non-competitive inhibition Increasing [S] cannot overcome inhibition Less E available, Vmax is lower, Km remains the same for available E

  13. Noncompetitive inhibition Km unaltered,Vmax decreased

  14. Non-competitive inhibitors as drugs • Fluoride: Non-competitive inhibitor of enolase • Non-nucleoside compounds as inhibitors of HIV RT

  15. Kinetics of irreversible inhibition

  16. EXAMPLES OF IRREVERSIBLE INHIBITORS AS DRUGS

  17. Amoxicillin and Clavulinic Acid

  18. Irreversible Inhibitors • Emphysema: Alpha-1-Antitrypsin deficiency—This protein inhibitor irreversibly inactivates elastase • Nerve Gas: Sarin—irreversibly inhibits acetylcholinesterase and conversion of acetylcholine to choline and acetic acid • Anticancer Drug: 5-Fluorouracil—irreversibly inhibits thymidylate synthetase

  19. Lecture 7-Learning objectives • Recognize the differences between competitive, non-competitive and irreversible inhibitors • Know how each of the inhibitors affects Km and Vmax • Know the importance of inhibition constant in drug design and discovery • Be knowledgeable about some of the drugs currently on the market

More Related