Synthesis of some pseudo-peptide analogs of thiol proteinase inhibitors.
Some pseudo-peptide analogs of thiol proteinase inhibitors were synthesized by a conventional solution method. Among them, Suc-Ala-Val-Val-Ala-psi-(CH2-NH)-Ala-pNA (peptide 1) and Suc-Ala-Val-Val-psi-(CH2-NH)-Ala-Ala-pNA (peptide 2) showed a stronger inhibitory activity compared with parent peptide such as Suc-Ala-Val-Val-Ala-Ala-pNA. In particular, peptide 2 was about 10-fold as active as the parent peptide (IC50 = 8 microM). Inserting psi-(CH2-NH) possibly makes the inhibitor less susceptible to papain and, as a result, produces more potent inhibition.
Iguchi
S
S
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Kawasaki
K
K
Okamoto
H
H
Umezawa
C
C
Okada
Y
Y
D002021:Buffers; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010206:Papain / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002021:Buffers; D009842:Oligopeptides; D011480:Protease Inhibitors; C119782:succinyl-alanyl-valyl-valyl-alanyl-psi(CH2NH)-alanyl-4-nitroanilide; C119783:succinyl-alanyl-valyl-valyl-psi(CH2NH)-alanyl-alanyl-4-nitroanilide; D003546:Cysteine Endopeptidases; D010206:Papain