Piperastatin A, a new selective serine carboxypeptidase inhibitor produced by actinomycete. I. Taxonomy, production, isolation and biological activities.
Piperastatin A (structure, N-formyl-allo Ile-Thr-Leu-Val-Pip-Leu-Pip, Pip = hexahydropyridadine-3-carboxylic acid; molecular weight, 809), a new inhibitor of serine carboxypeptidase was discovered in the fermentation broth of Streptomyces lavendofoliae MJ908-WF13. It was purified by activated charcoal chromatography, YMC gel ODS-A chromatography and centrifugal partition chromatography (CPC) by monitoring its inhibitory activity against carboxypeptidase Y (CP-Y), and finally obtained as colourless needles. Piperastatin A is a competitive inhibitor of the enzyme with Ki = 52 +/- 6.2 nM. Piperastatin A is a highly specific inhibitor of the serine carboxypeptidases, CP-Y and platelet deamidase with little effect on related enzymes, has no antimicrobial activity and has low toxicity.
Murakami
S
S
Institute of Microbial Chemistry, Tokyo, Japan.
Harada
S
S
Yamazaki
T
T
Takahashi
Y
Y
Hamada
M
M
Takeuchi
T
T
Aoyagi
T
T
D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043402:Cathepsin A; D002965:Classification; D004950:Esterases / Q000037:antagonists & inhibitors; D007700:Kinetics; D008049:Lipase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000378:metabolism*; D011724:Pyridazines / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*; D013379:Substrate Specificity
D009842:Oligopeptides; D010455:Peptides; D011480:Protease Inhibitors; D011724:Pyridazines; C103102:piperastatin A; D004950:Esterases; D008049:Lipase; D002268:Carboxypeptidases; D043402:Cathepsin A