Inhibition of metalloendopeptidases by 2-mercaptoacetyl-dipeptides

Eur J Biochem. 1983 Oct 17;136(1):151-4. doi: 10.1111/j.1432-1033.1983.tb07719.x.

Abstract

A series of 2-mercaptoacetyl-dipeptides, a potential group of metalloendopeptidase inhibitors, has been synthesized by coupling the N-hydroxysuccinimide ester of S-acetyl-2-mercaptoacetic acid with hydrophobic dipeptide methyl ester hydrochlorides, followed by hydrolysis with NaOH in aqueous methanol and acidification with HCl. Thus, the 2-mercaptoacetyl derivatives of L-phenylalanyl-L-leucine, L-leucyl-L-phenylalanine and L-leucyl-D-phenylalanine were prepared. The first two compounds inhibit effectively thermolysin from Bacillus thermoproteolyticus and a metalloendopeptidase isolated from Streptomyces griseus, with Ki values in the micromolar range or below. The third compound inhibits the two enzymes only poorly, showing the stereospecificity of the inhibition process. These inhibitors should provide a useful tool for the study of bacterial and mammalian metalloendopeptidases (or dipeptidyl carboxypeptidases) and for the assessment of their physiological role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Dipeptides / chemical synthesis*
  • Dipeptides / pharmacology
  • Endopeptidases / isolation & purification
  • Metalloendopeptidases
  • Protease Inhibitors* / chemical synthesis*
  • Streptomyces griseus / enzymology
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / pharmacology
  • Thermolysin / antagonists & inhibitors

Substances

  • Dipeptides
  • Protease Inhibitors
  • Sulfhydryl Compounds
  • Endopeptidases
  • Metalloendopeptidases
  • Thermolysin