Effect of HGF-like basic hexapeptides on angiogenesis

Microvasc Res. 2001 Nov;62(3):440-4. doi: 10.1006/mvre.2001.2354.

Abstract

The interaction of glycosaminoglycans (GAG) with peptides relies on noncovalent binding to basic amino acid sequences, for which a minimal requirement is a pentapeptide region in the protein and the sulfated and carboxyl region in the GAG. Since such sequences are present in the heparin-binding angiogenic cytokines, including hepatocyte growth factor (HGF), we have postulated that such small peptides may have biological activity. Two basic peptide regions of the beta chain of HGF (RYRNKH512-516, HHRGK645-649) exhibited significant antiangiogenic activity in vivo in the chorioallantoic membrane assay and showed some antiproliferative activity in vitro on normal human brain microvessel endothelial-but not on anchorage-independent endothelial-cells (Kaposi sarcoma). Basic HIV-TAT peptides and scrambled hexapeptides did not show similar activity, except for KRKRKR, indicating sequence specificity of the phenomena. An HGF-derived basic peptide, HHRGK, modulated tumor-induced angiogenesis in vivo by interfering with the morphogenic, but not with the proliferative, phase of the process. These observations suggest small basic peptides as a new class of angiogenesis modulators.

MeSH terms

  • Allantois / drug effects
  • Allantois / physiology
  • Animals
  • Brain / blood supply*
  • Brain / cytology
  • Cell Count
  • Cell Division / drug effects
  • Chick Embryo
  • Chorion / drug effects
  • Chorion / physiology
  • Cytokines / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Heparin / chemistry
  • Hepatocyte Growth Factor / chemistry*
  • Mice
  • Mice, SCID
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Peptides
  • Hepatocyte Growth Factor
  • Heparin