High-throughput screening of novel peptide inhibitors of an integrin receptor from the hexapeptide library by using a protein microarray chip.
Protein microarray is an emerging technology that makes high-throughput analysis possible for protein-protein interactions and analysis of proteome and biomarkers in parallel. The authors investigated the application of a novel protein microarray chip, ProteoChip, in new drug discovery. Integrin alpha(v)beta(3) microarray immobilized on the ProteoChip was employed to screen new active peptides against the integrin from multiple hexapeptide sublibraries of a positional scanning synthetic peptide combinatorial library (PS-SPCL). The integrin alpha(v)beta(3)-vitronectin interaction was successfully demonstrated on the integrin microarray in a dose-dependent manner and was inhibited not only by the synthetic RGD peptide but also by various integrin antagonists on the integrin microarray chip. Novel peptide ligands with high affinity to the integrin were also identified from the peptide libraries with this chip-based screening system by a competitive inhibition assay in a simultaneous and high-throughput fashion. The authors have confirmed antiangiogenic functions of the novel peptides thus screened through an in vitro and in vivo angiogenesis assay. These results provide evidence that the ProteoChip is a promising tool for high-throughput screening of lead molecules in new drug development.
Lee
Yoonsuk
Y
Proteogen, Inc., Seoul, Korea.
Kang
Dong-Ku
DK
Chang
Soo-Ik
SI
Han
Moon Hi
MH
Kang
In-Cheol
IC
D002465:Cell Movement / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D040081:Protein Array Analysis / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods; D040901:Proteomics; D014470:Umbilical Cord / Q000166:cytology
D039302:Integrin alphaVbeta3; D009842:Oligopeptides