1241047-37-9Relevant academic research and scientific papers
Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors
Di Cianni, Alessandra,Carotenuto, Alfonso,Brancaccio, Diego,Novellino, Ettore,Reubi, Jean Claude,Beetschen, Karin,Papini, Anna Maria,Ginanneschi, Mauro
supporting information; experimental part, p. 6188 - 6197 (2010/11/02)
A limited set of novel octreotide dicarba-analogues with non-native aromatic side chains in positions 7 and/or 10 were synthesized. Their affinity toward the ssts1-5 was determined. Derivative 4 exhibited a pan-somatostatin activity, except sst4, and derivative 8 exhibited high affinity and selectivity toward sst5. Actually, compound 8 has similar sst5 affinity (IC50 4.9 nM) to SRIF-28 and octreotide. Structure-activity relationships suggest that the Z geometry of the double-bond bridge is that preferred by the receptors. The NMR study on the conformations of these compounds in SDS-d25 micelles solution shows that all these analogues have the pharmacophore β-turn spanning Xaa 7-d-Trp8-Lys9-Yaa10 residues. Notably, the correlation between conformation families and affinity data strongly indicates that the sst5 selectivity is favored by a helical conformation involving the C-terminus triad, while a pan-SRIF mimic activity is based mainly on a conformational equilibrium between extended and folded conformational states.
Novel sst5-selective somatostatin dicarba-analogues: Synthesis and conformation-affinity relationships
D'Addona, Debora,Carotenuto, Alfonso,Novellino, Ettore,Piccand, Véronique,Reubi, Jean Claude,Di Cianni, Alessandra,Gori, Francesca,Papini, Anna Maria,Ginanneschi, Mauro
, p. 512 - 520 (2008/09/20)
We describe synthesis, conformational studies, and binding to the five somatostatin receptors (sst1-5) of a few analogues of the cyclic octapeptide octreotide (1), where the disulfide bridge was replaced by a dicarba group. These analogues were
