Patrick Marcotte

Active site-directed inactivation of cystathionine γ-synthetase and glutamic pyruvic transaminase by propargylglycine

Abstract The acetylenic amino acid propargylglycine (2-amino-4-pentynoate) irreversibly inactivates two pyridoxal-P dependent enzymes which generate substrate-derived beta carbanions during catalysis.

Modified peptides which display potent and specific inhibition of human renin

A new class of angiotensinogen analogues which contain heteroatom-methylene and retro-inverso amide bond replacements was synthesized and evaluated for renin inhibition. Selected compounds in the series were specific for renin over other aspartic proteinases, and the most potent inhibitor demonstrated hypotensive activity in a salt depleted monkey.

Renin inhibitors Improvements in the stability and biological activity of small peptides containing novel Leu‐Val replacements

We have designed a novel class of potent (0.3–7 nM) renin inhibitors which contain a dihydroxyethylene replacement for what is formally the Leu1O‐Val11 amide bond. Good potency (0.6 nM), water solubility (> 10 mg/ml at 37°C), stability toward degradation by chymotrypsin (t =82O min), and in vivo activity in a primate model (15% drop in mean arterial pressure in association with complete inhibition of plasma renin activity) are properties which have been incorporated into compound 10, an interesting new agent to be used in the study of hypertension.

Synthesis of α-hydroxy-β-acetylenic acids and their oxidation by and inactivation of flavoprotein oxidases

Five α-hydroxy-β-acetylenic acids have been prepared; all are active substrates for a mammalian flavoprotein oxidase, with only the C4 molecule a particularly effective suicide substrate.