title: The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.
abstract: Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to inhibit via formation of a sulfinanilide at Cys138.
authors.affiliation: SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. Dave_G_Smith@sbphrd.com
authors.forename: D G
authors.initials: DG
authors.lastname: Smith
authors.forename: A D
authors.initials: AD
authors.lastname: Gribble
authors.forename: D
authors.initials: D
authors.lastname: Haigh
authors.forename: R J
authors.initials: RJ
authors.lastname: Ife
authors.forename: P
authors.initials: P
authors.lastname: Lavery
authors.forename: P
authors.initials: P
authors.lastname: Skett
authors.forename: B P
authors.initials: BP
authors.lastname: Slingsby
authors.forename: R
authors.initials: R
authors.lastname: Stacey
authors.forename: R W
authors.initials: RW
authors.lastname: Ward
authors.forename: A
authors.initials: A
authors.lastname: West
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D003587:Cytomegalovirus / Q000201:enzymology*; D003586:Cytomegalovirus Infections; D006801:Humans; D006898:Hydroxylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D014357:Trypsin
chemical_list: D000890:Anti-Infective Agents; D006898:Hydroxylamines; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C071910:assemblin; D014357:Trypsin