Inhibition of metalloendopeptidases by 2-mercaptoacetyl-dipeptides
1983; Wiley; Volume: 136; Issue: 1 Linguagem: Inglês
10.1111/j.1432-1033.1983.tb07719.x
ISSN1432-1033
AutoresShmaryahu Blumberg, Zofia TAUBER,
Tópico(s)Protein Hydrolysis and Bioactive Peptides
ResumoA 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 K i 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.
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