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.

Zinc enzymology is, compared to some other current areas of metallobiochemistry, a maturing field, but in addition to further developments of structure-function relationships it has also provided a number of surprising new results and ideas in the last few years. In fact, the number of studies makes it impossible to provide a comprehensive review of the recent literature on zinc enzymology here, and the authors therefore focus on those zinc enzymes for which structure-function relationships are possible on the basis of structural and biochemical data. This means that, with a few exceptions, only zinc enzymes for which NMR or crystal structures are available are included here. Another seemingly simple, yet experimentally sometimes complex issue concerns the choice of which metalloenzyme is a zinc enzyme. Since there is in principle no difference in chemical catalysis by low-affinity compared to high-affinity metal sites, some of these enzymes are also included in this article, especially if they are or have been discussed as zinc enzymes, or are active with zinc. 552 refs.

David W. Cushman

Papers

Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung

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

Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids.

Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Importance of the COOH-terminal dipeptide sequence.

Enzymes of the Renin-Angiotensin System and their Inhibitors