A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.

https://science.sciencemag.org/content/sci/196/4288/441.full.pdf

Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents

https://digital.csic.es/bitstream/10261/63157/4/Gomez-Guillen-collagenreview_CSIC.pdf

Functional and bioactive properties of collagen and gelatin from alternative sources: A review

The influence of natural products upon drug discovery.

Renin-angiotensin system: biochemistry and mechanisms of action.

3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.

Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists

Dipeptides of the formula: ##EQU1## wherein n is an integer from 0 to 5, R1 is an alkyl, alkylaryl or alicyclic radical, and R2 is a cycloalkenyl radical, and, in addition, may be phenyl when n is 0. The carbon marked with an asterisk is always of the L-configuration. These compounds have a sweet taste and are useful as sweetening agents.

L-Aspartyl dipeptides as sweetening agents

Disclosed herein is a process for the utilization of certain peptides as angiotensin converting enzyme inhibitors.

Peptides as argiotensin converting enzyme inhibitors

New carboxyalkylacylamino acids which are derivatives of proline, pipecolic acid and azetidine-2-carboxylic acid and have the general formula ##STR1## are useful as angiotensin converting enzyme inhibitors.

N-carboxyalkanoyl derivatives of azetidine-2-carboxylic acid

Peptides of the formula Arg-A-Pro-Gly-B-Ser-A-B-Arg wherein A is Pro or beta H-Pro and B is Phe or beta H-Phe, provided at least one A or B is a beta -homoaminoacid, possess hypotensive activity and are more resistant to enzymatic degradation than the corresponding alpha -aminoacid peptide.

Miguel A. Ondetti

Papers

L-Aspartyl dipeptides as sweetening agents

Peptides as argiotensin converting enzyme inhibitors

N-carboxyalkanoyl derivatives of azetidine-2-carboxylic acid

Hypotensive {62 -homoaminoacid nonapeptides

Proton Nuclear Magnetic Resonance Study of Sccretin