Novel Octreotide Dicarba-analogues

In collaboration with:

European Institute of Oncology, Milano, Italy

We developed interesting biostable somatostatine analogues with a dicarba moiety replacing the disulfide bridge. Five analogues were synthesized by on-resin ring-closing metathesis (RCM) of linear heptapeptides containing two allylglycine residues. A new pharmacophore model for the five somatostatine receptors (sst5) was developed. The proposed pharmacophore model can be useful in designing highly selective peptide as well as nonpeptide ligands at the sst5 receptor.

Moreover in our ongoing efforts to develop new somatostatin (SRIF) ligands with improved stability and affinity toward somatostatin receptors, we have rationally designed and analyzed a set of  novel octreotide dicarba-peptide analogues with non-native aromatic side chains. In these peptides, the labile disulfide bridge was replaced by a dicarba-bridge, through the RCM reaction. Both pan- and selective-SRIF analogues are potentially useful for the diagnosis and internal radiotherapy of tumors.


Publications associées:

Novel sst5-selective somatostatin dicarba-analogues: synthesis and conformation-affinity relationships. D’Addona, D.; Carotenuto, A.; Novellino, E.; Piccand, V.; Reubi, J. C.; Di Cianni, A.; Gori, F.; Papini, A. M.; Ginanneschi, M. J. Med. Chem. 2008, 51, 512–520.

Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. Di Cianni, A.; Carotenuto, A.; Brancaccio, D.; Novellino, E.; Reubi, J. C.; Beetschen, K.; Papini, A. M.; Ginanneschi, M. J. Med. Chem. 2010, 53, 6188–6197.