title: Structure-based design of ketone-containing, tripeptidyl human rhinovirus 3C protease inhibitors.
abstract: Tripeptide-derived molecules incorporating C-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). An optimized example of such compounds displayed potent 3CP inhibition activity (K = 0.0045 microM) and in vitro antiviral properties (EC50=0.34 microM) when tested against HRV serotype-14.
authors.affiliation: Agouron Pharmaceuticals, Inc., San Diego, CA 92121, USA. psd@agouron.com
authors.forename: P S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: R
authors.initials: R
authors.lastname: Zhou
authors.forename: S E
authors.initials: SE
authors.lastname: Webber
authors.forename: T J
authors.initials: TJ
authors.lastname: Prins
authors.forename: A K
authors.initials: AK
authors.lastname: Kwok
authors.forename: K
authors.initials: K
authors.lastname: Okano
authors.forename: S A
authors.initials: SA
authors.lastname: Fuhrman
authors.forename: L S
authors.initials: LS
authors.lastname: Zalman
authors.forename: F C
authors.initials: FC
authors.lastname: Maldonado
authors.forename: E L
authors.initials: EL
authors.lastname: Brown
authors.forename: J W
authors.initials: JW
authors.lastname: Meador
authors.forename: A K
authors.initials: AK
authors.lastname: Patick
authors.forename: C E
authors.initials: CE
authors.lastname: Ford
authors.forename: M A
authors.initials: MA
authors.lastname: Brothers
authors.forename: S L
authors.initials: SL
authors.lastname: Binford
authors.forename: D A
authors.initials: DA
authors.lastname: Matthews
authors.forename: R A
authors.initials: RA
authors.lastname: Ferre
authors.forename: S T
authors.initials: ST
authors.lastname: Worland
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins
chemical_list: D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D007659:Ketones; D009842:Oligopeptides; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases