A novel integrin alpha5beta1 antagonistic peptide, A5-1, screened by Protein Chip system as a potent angiogenesis inhibitor.
Integrin alpha5beta1 immobilized on a ProteoChip was used to screen new antagonistic peptides from multiple hexapeptide sub-libraries of the positional scanning synthetic peptide combinatorial library (PS-SPCL). The integrin alpha5beta1-Fibronectin interaction was demonstrated on the chip. A novel peptide ligand, A5-1 (VILVLF), with high affinity to integrin alpha5beta1 was identified from the hexapeptide libraries with this chip-based screening method on the basis of a competitive inhibition assay. A5-1 inhibits the integrin-fibronectin interaction in a dose-dependent manner (IC(50); 1.56+/-0.28 microM. In addition, it inhibits human umbilical vein endothelial cell proliferation, migration, adhesion, tubular network formation, and bFGF-induced neovascularization in a chick chorioallantoic membrane. These results suggest that A5-1 will be a potent inhibitor of neovascularization.
Kim
Eung-Yoon
EY
BioChip Research Center, Hoseo University, Asan 336-795, Republic of Korea.
Bang
Ji Young
JY
Chang
Soo-Ik
SI
Kang
In-Cheol
IC
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D040081:Protein Array Analysis
D020533:Angiogenesis Inhibitors; D039081:Integrin alpha5beta1; D009842:Oligopeptides; C533691:valyl-isoleucyl-leucyl-valyl-leucyl-phenylalanine