Peptomeric analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds

Bioorg Med Chem. 2008 May 15;16(10):5644-52. doi: 10.1016/j.bmc.2008.03.075. Epub 2008 Apr 1.

Abstract

A series of linear and monocyclic analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds, modified by N-(4-aminobutyl)glycine (Nlys) and N-benzylglycine (Nphe), were obtained by the solid-phase method. Some of these peptomers displayed trypsin or chymotrypsin inhibitory activity. In contradiction to the literature data, in most analogues peptide bonds formed by these peptoid monomers were at least partially hydrolyzed by the experimental enzymes at two different pH (3.5 and 8.3). Nevertheless, the replacement of Phe present in the P(1) substrate specificity of linear inactive SFTI-1 analogue with Nphe, yielded a potent chymotrypsin inhibitor. The introduction of one cyclic element (a disulfide bridge or head-to-tail cyclization) to the analogues synthesized significantly increased their proteinase resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Helianthus / chemistry*
  • Hydrolysis
  • Molecular Sequence Data
  • Peptide Library
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology
  • Seeds / chemistry*
  • Solid Phase Extraction / methods
  • Time Factors
  • Trypsin / drug effects
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / isolation & purification*
  • Trypsin Inhibitors / pharmacology

Substances

  • Peptide Library
  • Peptides, Cyclic
  • SFTI-1 peptide, sunflower
  • Trypsin Inhibitors
  • Trypsin