Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase.
A series of keto-glutamine tetrapeptide analogs containing a 2-oxo-pyrrolidine ring as a glutamine side chain mimic were synthesized with both R and S configuration at the beta-carbon. Compounds bearing a phthalhydrazide moiety show improved reversible inhibition of HAV 3C proteinase in the low micromolar range.
Jain
Rajendra P
RP
Department of Chemistry, University of Alberta, Edmonton, AB, Canada T6G 2G2.
Vederas
John C
JC
D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases; D005973:Glutamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D030041:Hepatitis A virus / Q000187:drug effects* / Q000201:enzymology; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis; D010793:Phthalazines / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
D009842:Oligopeptides; D010793:Phthalazines; D011480:Protease Inhibitors; D011759:Pyrrolidines; D014764:Viral Proteins; D005973:Glutamine; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; C032519:pyrrolidine