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Journal of Biomolecular Screening
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High-Throughput Screening of Novel Peptide Inhibitors of an Integrin Receptor from the Hexapeptide Library by Using a Protein Microarray Chip

Yoonsuk Lee

Proteogen, Inc., Seoul, Korea.

Dong-Ku Kang

Soo-Ik Chang

Department of Biochemistry, Chungbuk National University, Cheongju, Korea.

Moon Hi Han

Proteogen, Inc., Seoul, Korea.

In-Cheol Kang

Protein Chip Research Center, Biotechnology Research Institute, Chungbuk National University, Cheongju 361-763, Korea (Republic)ickang{at}chungbuk.ac.kr

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, Proteo Chip, in new drug discovery. Integrin {alpha}vß3 microarray immobilized on the Proteo Chip 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}vß3-vitronectin interaction was successfully demonstrated on the integrin microarray in a dose-dependent manner andwas inhibited not only by the syntheticRGDpeptide 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 highthroughput 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 Proteo Chip is a promising tool for highthroughput screening of lead molecules in new drug development.

Key Words: Proteo Chip • protein microarray • ProLinker • integrin • PS-SPCL

Journal of Biomolecular Screening, Vol. 9, No. 8, 687-694 (2004)
DOI: 10.1177/1087057104268125
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