Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2291-4. doi: 10.1016/s0960-894x(00)00460-1.

Abstract

A method for the solid-phase synthesis of P1 arginine containing peptides via attachment of the arginine side-chain guanidine group is described. This procedure is applied to the preparation of a tetrapeptide, P1 arginine aminocoumarin PS-SCL. This library was validated by using it to determine the P4-P2 specificity for thrombin and comparing the results to the known thrombin subsite specificity. This is the first reported example of a PS-SCL library containing a P1 arginine.

MeSH terms

  • Arginine*
  • Coumarins*
  • Humans
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Peptide Library*
  • Protein Conformation
  • Serine Endopeptidases / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thrombin / metabolism*
  • Trypsin / metabolism*

Substances

  • Coumarins
  • Oligopeptides
  • Peptide Library
  • Arginine
  • Serine Endopeptidases
  • Trypsin
  • Thrombin