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. doi: 10.1016/s1074-5521(02)00129-1.


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.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Binding, Competitive
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Molecular Sequence Data
  • Peptide Library*
  • Peptides / chemistry
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Protein Structure, Secondary
  • Receptors, Cell Surface / metabolism
  • Solubility
  • Tumor Cells, Cultured


  • Insulin-Like Growth Factor Binding Proteins
  • Peptide Library
  • Peptides
  • Receptors, Cell Surface
  • Insulin-Like Growth Factor I

Associated data

  • PDB/1LB7