Synthesis and binding affinities for sst receptors of cyclic peptoid SRIF-mimetics.

Cécile Caumes (1) , Thomas Hjelmgaard (2) , Olivier Roy (1) , Morgane Reynaud (3) , Denis Servent (3) , Claude Taillefumier (1) , Sophie Faure (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique
2 Department of Basic Sciences and Environment
3 IBITECS - Institut de Biologie et de Technologies de Saclay

Mimicking the tetradecapeptide somatostatin through the design of novel non-peptide small molecules is needed for developing analogues with selective or universal affinity for human somatostatin receptors (hsst1-5) and improved pharmacological properties. We report the synthesis and evaluation of the binding potential of the first all-peptoid SRIF (somatotropin release-inhibiting factor) analogues. Cyclic β and mixed α/β tetra- or pentapeptoids were efficiently obtained by macrocyclisation of the corresponding linear peptoids. In vitro competition binding experiments using [125I]-somatostatin were performed on this first generation of peptoids mimicking the SRIF pharmacophore (Phe7-(D)Trp8-Lys9-Thr10). The selectivity profiles of cyclic compounds 1 to 4 were similar with higher affinity for the sst3, sst5 and sst4 receptors and lower potency on sst1 and sst2 subtypes.

Cécile Caumes, Thomas Hjelmgaard, Olivier Roy, Morgane Reynaud, Denis Servent, et al.. Synthesis and binding affinities for sst receptors of cyclic peptoid SRIF-mimetics.. Med. Chem. Commun., 2012, 3, 1531-1535, 2012, 3, pp.1531-1535. ⟨hal-00787235⟩