Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg- isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg- isoDGR-( NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg- isoDGR-( NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.
N-Methylation of isoDGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent / Kapp, Tobias G; Di Leva, Francesco Saverio; Notni, Johannes; Räder, Andreas F B; Fottner, Maximilian; Reichart, Florian; Reich, Dominik; Wurzer, Alexander; Steiger, Katja; Novellino, Ettore; Marelli, Udaya Kiran; Wester, Hans-Jürgen; Marinelli, Luciana; Kessler, Horst. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 61:6(2018), pp. 2490-2499. [10.1021/acs.jmedchem.7b01752]
N-Methylation of isoDGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent
Di Leva, Francesco SaverioCo-primo
;Novellino, Ettore;Marinelli, Luciana
Penultimo
;
2018
Abstract
Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg- isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg- isoDGR-( NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg- isoDGR-( NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.File | Dimensione | Formato | |
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