1LB7

IGF-F1-1, A PEPTIDE ANTAGONIST OF IGF-1

1LB7 の概要

• エントリーDOI: 10.2210/pdb1lb7/pdb
• 分子名称: IGF-1 ANTAGONIST F1-1 (1 entity in total)
• 機能のキーワード: loop-helix, disulfide, de novo protein
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1879.22

構造登録者

Deshayes, K.,Schaffer, M.L.,Skelton, N.J.,Nakamura, G.R.,Kadkhodayan, S.,Sidhu, S.S. (登録日: 2002-04-02, 公開日: 2002-06-19, 最終更新日: 2024-10-30)

主引用文献

Deshayes, K.,Schaffer, M.L.,Skelton, N.J.,Nakamura, G.R.,Kadkhodayan, S.,Sidhu, S.S.
Rapid identification of small binding motifs with high-throughput phage display: discovery of peptidic antagonists of IGF-1 function.
Chem.Biol., 9:495-505, 2002

PubMed Abstract: A panel of 22 naïve 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.

PubMed: 11983338
DOI: 10.1016/S1074-5521(02)00129-1

実験手法

SOLUTION NMR