Design of bivalent ligands using hydrogen bond linkers: synthesis and evaluation of inhibitors for human beta-tryptase

Bioorg Med Chem Lett. 2004 Dec 20;14(24):6053-6. doi: 10.1016/j.bmcl.2004.09.065.

Abstract

We exploit the concept of using hydrogen bonds to link multiple ligands for maintaining simultaneous interactions with polyvalent binding sites. This approach is demonstrated by the syntheses and evaluation of pseudo-bivalent ligands as potent inhibitors of human beta-tryptase.

MeSH terms

  • Binding Sites
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Humans
  • Hydrogen Bonding
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Molecular Weight
  • Serine Endopeptidases / drug effects*
  • Structure-Activity Relationship
  • Tryptases

Substances

  • Enzyme Inhibitors
  • Ligands
  • Serine Endopeptidases
  • Tryptases