Structural highlights
Publication Abstract from PubMed
A panel of 22 naive peptide libraries was constructed in a polyvalent phage display format and sorted against insulin-like growth factor-1 (IGF-1). The libraries were pooled to achieve a total diversity of 4.4 x 10(11). After three rounds of selection, the majority of the phage clones bound specifically to IGF-1, with a disulfide-constrained CX(9)C scaffold dominating the selection. Four monovalently displayed sub-libraries were designed on the basis of these conserved motifs. Sub-library maturation in a monovalent format yielded an antagonistic peptide that inhibited the interactions between IGF-1 and two cell-surface receptors and those between IGF-1 and two soluble IGF binding proteins with micromolar potency. NMR analysis revealed that the peptide is highly structured in the absence of IGF-1, and peptides that preorganize the binding elements were selected during the sorting.
Rapid identification of small binding motifs with high-throughput phage display: discovery of peptidic antagonists of IGF-1 function.,Deshayes K, Schaffer ML, Skelton NJ, Nakamura GR, Kadkhodayan S, Sidhu SS Chem Biol. 2002 Apr;9(4):495-505. PMID:11983338[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deshayes K, Schaffer ML, Skelton NJ, Nakamura GR, Kadkhodayan S, Sidhu SS. Rapid identification of small binding motifs with high-throughput phage display: discovery of peptidic antagonists of IGF-1 function. Chem Biol. 2002 Apr;9(4):495-505. PMID:11983338
