Polymer-supported approach for solution-phase synthesis of cysteine trap protease inhibitors: procedure for straightforward optimization of the P1-P1' pocket

J Comb Chem. 2002 Jan-Feb;4(1):49-55. doi: 10.1021/cc010037v.

Abstract

Peptide-based reversible and irreversible cysteine proteases inhibitors are well reported in the literature. Many of these compounds have an electrophilic carbonyl group as a cysteine trap in the place of a scissile amide moiety of the natural substrate. As a common mechanism strategy, we have designed a probe library of a cysteine trap for rapid optimization of P1-P1' pockets of different cysteine proteases. The synthesis of this library using a straightforward methodology based on polymer-supported reagents and scavengers to avoid tedious purification steps has been achieved. For the selective monobromination of diazo ketones, preparation of a new supported reagent, piperidinoaminomethylpolystyrene hydrobromide, is also described.

MeSH terms

  • Binding Sites
  • Combinatorial Chemistry Techniques / methods*
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / chemistry
  • Diazonium Compounds / chemical synthesis
  • Diazonium Compounds / chemistry
  • Drug Design
  • Molecular Mimicry
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Polymers / chemistry

Substances

  • Cysteine Proteinase Inhibitors
  • Diazonium Compounds
  • Molecular Probes
  • Oligopeptides
  • Polymers