N-Methylation of isoDGR Peptides: Discovery of a Selective ?5?1-Integrin Ligand as a Potent Tumor Imaging Agent.

Specific targeting of the integrin subtype ?5?1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective ?5?1/?v?6 peptide c(phg- isoDGR-k) into a potent peptidic RGD binding ?5?1 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 ?5?1 integrin expression in a M21 mouse xenograft.     «

Specific targeting of the integrin subtype ?5?1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective ?5?1/?v?6 peptide c(phg- isoDGR-k) into a potent peptidic RGD binding ?5?1 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...     »