Synthesis and biochemical evaluation of a cyclic RGD oxorhenium complex as new ligand of αVβ3 integrin

We report the design of a new ligand of integrins that might be used for the molecular imaging of tumor neoangiogenesis. For this purpose, we designed a modified RGD tripeptide bearing a N-terminal N-bis(thioethyl)glycinate (NS2) motif and a thioethyl moiety at the C-terminus. Simultaneous coordination of an oxorhenium core by the NS2 and thioethyl moieties led to peptide cyclization and gave the corresponding monomers 13a and b (major isomer) resulting from the syn/anti-isomerism, along with dimers' species 16a and b. Cyclometallated peptide 13b showed the most promising activity with an IC50 of 86 nM for integrin αVβ3 whereas it binds integrin αIIbβ3 with an affinity lower by an order of magnitude. Labeling with [99mTc]oxotechnetium gluconate led exclusively to complex 17, the equivalent of compound 13b, which displayed satisfactory stabilities in mice plasma and towards glutathione.

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