Lysyl 4-aminobenzoic acid derivatives as potent small molecule mimetics of plasminogen kringle 5

Bioorg Med Chem Lett. 2004 Feb 23;14(4):965-6. doi: 10.1016/j.bmcl.2003.12.034.

Abstract

Kringle 5, a proteolytic fragment of human plasminogen has been shown to potently inhibit angiogenesis. The tetrapeptide KLYD derived from kringle 5 has been shown to capture many activities of kringle 5 in vitro. Further simplification has been achieved by replacement of the two central amino acids with a 4-aminobenzoic acid spacer group. Molecules displaying the required recognition groups on this core show similar in vitro properties to kringle 5, and are able to displace radiolabeled protein from a high affinity binding site on endothelial cells.

MeSH terms

  • 4-Aminobenzoic Acid / chemistry*
  • Cell Migration Inhibition
  • Cell Movement / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Humans
  • Kringles*
  • Molecular Mimicry*
  • Molecular Structure
  • Plasminogen / chemistry
  • Plasminogen / genetics
  • Plasminogen / pharmacology*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / pharmacology
  • para-Aminobenzoates*

Substances

  • Vascular Endothelial Growth Factor A
  • para-Aminobenzoates
  • Plasminogen
  • 4-Aminobenzoic Acid