Conformationally constrained mimetics of laminin peptide YIGSR as precursors for antimetastatic disintegrins

J Med Chem. 2009 Dec 24;52(24):7966-9. doi: 10.1021/jm901212n.

Abstract

Conformationally constrained mimetics of the laminin cell-adhesion site, YIGSR, are described. The site is the natural antagonist of the integrin-associated laminin receptor 1 (LAMR1) known to mediate metastatic tumor adhesion. The attachment of selected metastatic cell lines toward the constrained antagonists has been assessed. Observed differential responses prompted by folding preferences of the mimetics revealed stronger attachment activities for turnlike structures. The results permit the conformational design of antimetastatic disintegrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • Cell Line, Tumor
  • Disintegrins / chemistry*
  • Fibrosarcoma / drug therapy
  • Fibrosarcoma / pathology
  • HeLa Cells
  • Humans
  • Laminin / chemistry*
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / pathology
  • Mice
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology
  • Protein Conformation
  • Receptors, Laminin / antagonists & inhibitors
  • Ribosomal Proteins

Substances

  • Antineoplastic Agents
  • Disintegrins
  • Laminin
  • Oligopeptides
  • Peptides, Cyclic
  • RPSA protein, human
  • Receptors, Laminin
  • Ribosomal Proteins
  • tyrosyl-isoleucyl-glycyl-seryl-arginine