Effects of YM-51084 and YM-51085, new inhibitors produced by Streptomyces sp. Q21705, on cathepsin L.
The structures of YM-51084 and YM-51085, new protease inhibitors produced by Streptomyces sp. Q21705, were determined by 1H- and 13C-NMR and mass spectrometry. Both were characterized by the basic structures of an acyl-tripeptide. YM-51084 was elucidated to be isovaleryl-tyrosyl-valyl-phenylalaninal and YM-51085 was the reduced phenylalaninol form of YM-51084. These compounds proved to strongly inhibit human kidney cathepsin L; the IC50 values being 9.6 x 10(-9) M and 3.5 x 10(-7) M, respectively.
Teramura
K
K
Drug Serendipity Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd, Tokyo, Japan.
Orita
M
M
Matsumoto
H
H
Yasumuro
K
K
Abe
K
K
D002247:Carbon Isotopes; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000737:chemistry; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000737:chemistry; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010450:Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006859:Hydrogen; D007668:Kidney / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009842:Oligopeptides / Q000494:pharmacology*; D010206:Papain / Q000037:antagonists & inhibitors / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment / Q000379:methods; D013302:Streptomyces / Q000737:chemistry*
D002247:Carbon Isotopes; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C107449:YM 51084; C107450:YM 51085; D006859:Hydrogen; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D010206:Papain