Lysyl 4-aminobenzoic acid derivatives as potent small molecule mimetics of plasminogen kringle 5.
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.
Sheppard
George S
GS
Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Park Road, Abbott Park, IL 60064, USA. george.sheppard@abbott.com
Kawai
Megumi
M
Craig
Richard A
RA
Davidson
Donald J
DJ
Majest
Sandra M
SM
Bell
Randy L
RL
Henkin
Jack
J
D010129:4-Aminobenzoic Acid / Q000737:chemistry*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018082:Kringles; D018716:Molecular Mimicry; D015394:Molecular Structure; D010958:Plasminogen / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D062366:para-Aminobenzoates
D042461:Vascular Endothelial Growth Factor A; D062366:para-Aminobenzoates; D010958:Plasminogen; D010129:4-Aminobenzoic Acid