A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.

@article{Shrivastava2005ADS,
  title={A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.},
  author={Ajay Shrivastava and Mathew A von Wronski and Aaron K. Sato and Dan Dransfield and Dan Sexton and Niculina Bogdan and Rajasekharan Pillai and Palaniappa Nanjappan and Benben Song and Eugene Marinelli and Daniel deOliveira and C Luneau and Mary Devlin and A. Muruganandam and Aida Abujoub and Gene Connelly and Qing Li Wu and Greg P Conley and Q Chang and Michael F Tweedle and Robert Charles Ladner and Rolf E. Swenson and Adrian D. Nunn},
  journal={Protein engineering, design & selection : PEDS},
  year={2005},
  volume={18 9},
  pages={417-24}
}
We describe a novel and general way of generating high affinity peptide (HAP) binders to receptor tyrosine kinases (RTKs), using a multi-step process comprising phage-display selection, identification of peptide pairs suitable for hetero-dimerization (non-competitive and synergistic) and chemical synthesis of heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6- to 500-fold) than either of… CONTINUE READING

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