Synthesis of tripeptide chloromethyl ketones and examination of their inhibitory effects on plasmin and plasma kallikrein.
With the aim of obtaining selective synthetic inhibitors of plasmin and plasma kallikrein, D-Ile-Phe-Lys-CH2Cl, Ile-Phe-Lys-CH2Cl, D-Ile-Phe-Arg-CH2Cl and Ile-Phe-Arg-CH2Cl were synthesized and their inhibitory activity against plasmin, plasma kallikrein and other trypsin-like serine proteinases was examined. Among them, D-Ile-Phe-Arg-CH2Cl exhibited a highly selective inhibitory activity against plasma kallikrein, yet D-Ile-Phe-Lys-CH2Cl exhibited nearly the same order of inhibitory activity against plasmin as well as plasma kallikrein.
Tsuda
Y
Y
Teno
N
N
Okada
Y
Y
Wanaka
K
K
Bohgaki
M
M
Hijikata-Okunomiya
A
A
Okamoto
U
U
Naito
T
T
Okamoto
S
S
D000590:Amino Acid Chloromethyl Ketones / Q000138:chemical synthesis*; D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D003864:Depression, Chemical; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000097:blood*; D008969:Molecular Sequence Data
D000590:Amino Acid Chloromethyl Ketones; C063352:isoleucyl-phenylalanyl-arginine chloromethyl ketone; C063351:isoleucyl-phenylalanyl-lysine chloromethyl ketone; D007610:Kallikreins; D005341:Fibrinolysin