The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.
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.
Smith
D G
DG
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. Dave_G_Smith@sbphrd.com
Gribble
A D
AD
Haigh
D
D
Ife
R J
RJ
Lavery
P
P
Skett
P
P
Slingsby
B P
BP
Stacey
R
R
Ward
R W
RW
West
A
A
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
D000890:Anti-Infective Agents; D006898:Hydroxylamines; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C071910:assemblin; D014357:Trypsin