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 journalArticle

65 Citations (Scopus)

Abstract

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
Volume3
DOIs
Publication statusPublished - 13-02-2012

Fingerprint

Peptide Nucleic Acids
nucleic acids
peptides
Display devices
Integrins
Ligands
ligands
Extracellular Matrix
lysine
metastasis
matrices
cells
Scaffolds
Lysine
attachment
affinity
Melanoma
cancer
Neoplasm Metastasis
Peptides

All Science Journal Classification (ASJC) codes

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

Cite this

Englund, E. A., Wang, D., Fujigaki, H., Sakai, H., Micklitsch, C. M., Ghirlando, R., ... Appella, D. H. (2012). Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds. Nature Communications, 3, [614]. https://doi.org/10.1038/ncomms1629
Englund, Ethan A. ; Wang, Deyun ; Fujigaki, Hidetsugu ; Sakai, Hiroyasu ; Micklitsch, Christopher M. ; Ghirlando, Rodolfo ; Martin-Manso, Gema ; Pendrak, Michael L. ; Roberts, David D. ; Durell, Stewart R. ; Appella, Daniel H. / Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds. In: Nature Communications. 2012 ; Vol. 3.
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Englund, EA, Wang, D, Fujigaki, H, Sakai, H, Micklitsch, CM, Ghirlando, R, Martin-Manso, G, Pendrak, ML, Roberts, DD, Durell, SR & Appella, DH 2012, 'Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds', Nature Communications, vol. 3, 614. https://doi.org/10.1038/ncomms1629

Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds. / Englund, Ethan A.; Wang, Deyun; Fujigaki, Hidetsugu; Sakai, Hiroyasu; Micklitsch, Christopher M.; Ghirlando, Rodolfo; Martin-Manso, Gema; Pendrak, Michael L.; Roberts, David D.; Durell, Stewart R.; Appella, Daniel H.

In: Nature Communications, Vol. 3, 614, 13.02.2012.

Research output: Contribution to journalArticle

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