Cyclic RGD-Containing functionalized azabicycloalkane peptides as potent integrin antagonists for tumor targeting

Leonardo Manzoni, Laura Belvisi, Daniela Arosio, Monica Civera, Michael Pilkington-Miksa, Donatella Potenza, Andrea Caprini, Elena M V Araldi, Eugenia Monferini, Monica Mancino, Francesca Podesta, Carlo Scolastico

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclic RGD-contaning functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe the synthesis and in vitro screening of these RGD derivatives, as well as the determination of their conformational properties in solution by spectro-scopic and computational methods. Docking studies with the X-ray crystal structure of the extracellular domain of integrin αvβ3were also performed to elucidate the structural binding requirements and to rationalize the biological results. One compound in particular was found to be the best αvβ3 integrin binder (IC50 = 53.7 nM) among the new functionalized RGD cyclic peptides, thus emerging as a promising candidate for co-valent bonding and selective homing of useful functional units.

Original languageEnglish
Pages (from-to)615-632
Number of pages18
JournalChemMedChem
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 17 2009

Keywords

  • Azabicycloalkanes
  • Inhibitors
  • Integrins
  • Peptidomimetics
  • RGD motif

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

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