BPS 2110 Lecture Notes - Lecture 4: Dd-Transpeptidase, Bergamottin, Lactam
19 Dec 2019
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Document Summary
Discovered in 1976 the worked against streptomyces clavuligerus. Not an antibiotic - dont inhibit transpeptidase or kill bacteria. useful for drugs that are susceptible to -lactamase. Selectivity: active site of transpeptidase is too large but size of -lactamase is perfect. Transpeptidase normally has very large substrate (cross link precursor) but this has no side chain on -lactam ring, so it will not fill enough of transpeptidase pocked to give effective binding and inhibition. Binds loosely to transpeptidase but strongly to -lactamase. Clinical use use in combination with -lactam that"s sensitive to -lactamase. Clavulanic acid: protects antibiotic from resistance enzyme, inhibits -lactamase glues to -lactamase and prevents it from interacting with -lactam ring of penicillin. Drug-drug interactions: one drug changes bioavailability of another. Penicillin not bioavailable without clavulanic acid because it gets destroyed by -lactamase without it. Grapefruit contains bergamottin which inhibits enzymes used in the liver. Metabolite irreversibly binds a glutamine on cyp450 deactivated.
