αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology

Title:αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology

Volume: 16 Issue: 3

Author(s): Alberto Dal Corso, Luca Pignataro, Laura Belvisi and Cesare Gennari

Affiliation:

Keywords: Anticancer Prodrugs, Drug Targeting, Integrins, Peptidomimetics, RGD, Small Molecule-Drug Conjugates.

Abstract: Covalent conjugation of anticancer drugs to targeting carriers (e.g., antibodies or small molecules) capable of selectively binding to tumor-specific antigens, is emerging as a successful strategy to overcome the drawbacks of traditional chemotherapy. Due to its overexpression on blood vessels of human tumors, αvβ3 integrin is one of the most studied receptors of tumor-targeted therapeutics: several peptides and peptidomimetics, bearing the RGD (Arg-Gly-Asp) recognition sequence, have been developed as integrin ligands and linked to different anticancer drugs. The resulting integrin- targeted small molecule-drug conjugates (SMDCs) are able to release the cytotoxic agents upon cleavage of a linker under specific conditions (i.e., hydrolysis, enzymatic action or reduction). Despite the significant efforts made in this field, αvβ3 integrin-targeted SMDCs are still far from the clinic. In this review, we survey this approach with a special focus on the different linkers employed and the reported biological activities in vitro and in vivo.

Cite this article as:

Dal Corso Alberto, Pignataro Luca, Belvisi Laura and Gennari Cesare, αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology, Current Topics in Medicinal Chemistry 2016; 16 (3) . https://dx.doi.org/10.2174/1568026615666150701114343