Ring size of somatostatin analogues (ODT-8) modulates receptor selectivity and binding affinity.

Research paper by Judit J Erchegyi, Christy Rani R CR Grace, Manoj M Samant, Renzo R Cescato, Veronique V Piccand, Roland R Riek, Jean Claude JC Reubi, Jean E JE Rivier

Indexed on: 16 Apr '08Published on: 16 Apr '08Published in: Journal of Medicinal Chemistry


The synthesis, biological testing, and NMR studies of several analogues of H-c[Cys (3)-Phe (6)-Phe (7)-DTrp (8)-Lys (9)-Thr (10)-Phe (11)-Cys (14)]-OH (ODT-8, a pan-somatostatin analogue, 1) have been performed to assess the effect of changing the stereochemistry and the number of atoms in the disulfide bridge on binding affinity. Cysteine at positions 3 and/or 14 (somatostatin numbering) were/was substituted with d-cysteine, norcysteine, D-norcysteine, homocysteine, and/or D-homocysteine. The 3D structure analysis of selected partially selective, bioactive analogues (3, 18, 19, and 21) was carried out in dimethylsulfoxide. Interestingly and not unexpectedly, the 3D structures of these analogues comprised the pharmacophore for which the analogues had the highest binding affinities (i.e., sst 4 in all cases).