Design and synthesis of redox stable analogues of sunflower trypsin inhibitors (SFTI-1) on solid support, potent inhibitors of matriptase

Org Lett. 2007 Jan 4;9(1):9-12. doi: 10.1021/ol0621497.

Abstract

[structure: see text] Matriptase is a member of the emerging class of type II transmembrane serine proteases. It was found that the sunflower trypsin inhibitor (SFTI-1), isolated from sunflower seeds, inhibits matriptase with a subnanomolar Ki of 0.92 nM. On the basis of this result, we designed and synthesized its proteolytically stable analogues, SFTI-2 and SFTI-3. SFTI-3 exhibited very good binding affinity to matriptase, and it was metabolically stable.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cyclization
  • Drug Design*
  • Helianthus / chemistry*
  • Molecular Structure
  • Oxidation-Reduction
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Trypsin Inhibitors / chemistry*

Substances

  • Peptides
  • Serine Proteinase Inhibitors
  • Trypsin Inhibitors
  • Serine Endopeptidases
  • matriptase