Isoaspartate-glycine-arginine: A new tumor vasculature-targeting motif

Flavio Curnis, Angelina Sacchi, Anna Gasparri, Renato Longhi, Angela Bachi, Claudio Doglioni, Claudio Bordignon, Catia Traversari, Gian Paolo Rizzardi, Angelo Corti

Research output: Contribution to journalArticlepeer-review


Asparagine deamidation in peptides or in fibronectin fragments containing the asparagine-glycine-arginine sequence generates isoaspartate-glycine-arginine (isoDGR), a new αvβ3 integrin-binding motif. Because αvβ3 is expressed in angiogenic vessels, we hypothesized that isoDGR-containing peptides could be exploited as ligands for targeted delivery of drugs to tumor neovasculature. We found that a cyclic CisoDGRC peptide coupled to fluorescent nanoparticles (quantum dots) could bind αvβ3 integrin and colocalize with anti-CD31, anti-αvβ3, and anti-α5β1 antibodies in human renal cell carcinoma tissue sections, indicating that this peptide could efficiently recognize endothelial cells of angiogenic vessels. Using CisoDGRC fused to tumor necrosis factor α (TNF) we observed that ultralow doses (1-10 pg) of this product (called isoDGR-TNF), but not of TNF or CDGRC-TNF fusion protein, were sufficient to induce antitumor effects when administered alone or in combination with chemotherapy to tumor-bearing mice. The antitumor activity of isoDGR-TNF was efficiently inhibited by coadministration with an excess of free CisoDGRC, as expected for ligand-directed targeting mechanisms.These results suggest that isoDGR is a novel tumor vasculature-targeting motif.P eptides containing isoDGR could be exploited as ligands for targeted delivery of drugs, imaging agents, or other compounds to tumor vasculature.

Original languageEnglish
Pages (from-to)7073-7082
Number of pages10
JournalCancer Research
Issue number17
Publication statusPublished - Sep 1 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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