Novel diphenyl esters of peptidyl alpha-aminoalkylphosphonates as inhibitors of chymotrypsin and subtilisin.
The activities of novel Cbz-N-protected alpha-aminophosphonic phenyl esters, analogs of leucine (1-15) and phenylalanine (17-29), which are substituted at the phenyl ester rings, as well as of their peptidic derivatives (31-43), were investigated for their inhibitory effects on chymotrypsin and subtilisin. The chemical nature and position of the examined substituents clearly demonstrated a strong structure-activity relationship. Among all synthesized compounds the most potent phosphonic-type inhibitors of subtilisin and chymotrypsin were identified, with k(2)/K(i) values 114,380 M(-1)s(-1) and 307,380 M(-1)s(-1), respectively.
Pietrusewicz
Ewa
E
Chemistry Department, Wrocław University of Technology, Wrocław, Poland.
Sieńczyk
Marcin
M
Oleksyszyn
Józef
J
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013381:Subtilisins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000588:Amines; D001713:Biphenyl Compounds; D002918:Chymotrypsin; D004952:Esters; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010455:Peptides; D015842:Serine Proteinase Inhibitors; D013381:Subtilisins; C010574:biphenyl