Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds

Ethan A. Englund, Deyun Wang, Hidetsugu Fujigaki, Hiroyasu Sakai, Christopher M. Micklitsch, Rodolfo Ghirlando, Gema Martin-Manso, Michael L. Pendrak, David D. Roberts, Stewart R. Durell, Daniel H. Appella

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


Multivalent effects dictate the binding affinity of multiple ligands on one molecular entity to receptors. Integrins are receptors that mediate cell attachment through multivalent binding to peptide sequences within the extracellular matrix, and overexpression promotes the metastasis of some cancers. Multivalent display of integrin antagonists enhances their efficacy, but current scaffolds have limited ranges and precision for the display of ligands. Here we present an approach to studying multivalent effects across wide ranges of ligand number, density, and three-dimensional arrangement. Using L-lysine γ-substituted peptide nucleic acids, the multivalent effects of an integrin antagonist were examined over a range of 1-45 ligands. The optimal construct improves the inhibitory activity of the antagonist by two orders of magnitude against the binding of melanoma cells to the extracellular matrix in both in vitro and in vivo models.

Original languageEnglish
Article number614
JournalNature communications
Publication statusPublished - 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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