Angiotensin-converting enzyme inhibitors: synthesis and biological activity of acyl tripeptide analogues of enalapril.

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Greenlee WJ, Allibone PL, Perlow DS, Patchett AA, Ulm EH, Vassil TC

Angiotensin-converting enzyme inhibitors: synthesis and biological activity of acyl tripeptide analogues of enalapril.

J Med Chem. 1985 Apr;28(4):434-42.

PubMed ID

2984419 [ View in PubMed

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Abstract

The synthesis and biological activity of a series of inhibitors of angiotensin-converting enzyme (EC 3.4.15.1) are described. Incorporation of the substituted N-carboxymethyl dipeptide design of enalapril (MK-421) into acyl tripeptides and larger peptides yielded potent inhibitors of the enzyme. These can be viewed as substrate analogues in which the carbonyl of the scissile peptide bond is replaced by a CHCO2H group. Several of the analogues described possess inhibitory potency equal to that of enalaprilat (MK-422), but none achieves an increase in potency which would demonstrate additional binding interactions contributed by the extended peptide chain. Application of the design described may be useful for inhibition of other metallopeptidases.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	20	N/A	N/A	Details