The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives

Bioorg Med Chem Lett. 1999 Nov 1;9(21):3137-42. doi: 10.1016/s0960-894x(99)00539-9.

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.

MeSH terms

  • Amino Acid Sequence
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / pharmacology
  • Binding Sites
  • Cytomegalovirus / enzymology*
  • Cytomegalovirus Infections
  • Humans
  • Hydroxylamines / chemical synthesis*
  • Hydroxylamines / pharmacology
  • Mass Spectrometry
  • Molecular Sequence Data
  • Molecular Structure
  • Peptide Fragments / chemistry
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / pharmacology
  • Trypsin

Substances

  • Anti-Infective Agents
  • Hydroxylamines
  • Peptide Fragments
  • Serine Proteinase Inhibitors
  • Serine Endopeptidases
  • assemblin
  • Trypsin