[摘要]：H-DPhe2-c[Cys3-Phe7-DTrp8-Lys9-Thr10-Cys14]-Thr15-NH2 (1) (a somatostatin agonist, SRIF numbering) and H-Cpa2-c[DCys3-Tyr7-DTrp8-Lys9-Thr10-Cys14]-Nal15-NH2 (4) (a somatostatin antagonist) are based on the structure of octreotide that binds to three somatostatin receptor subtypes (sst2/3/5) with significant binding affinity. Analogs of 1 and 4 were synthesized with norcysteine (Ncy), homocysteine (Hcy), or D-homocysteine (DHcy) at positions 3 and/or 14. Introducing Ncy at positions 3 and 14 constrained the backbone flexibility, resulting in loss of binding affinity at all ssts. The introduction of Hcy at positions 3 and 14 improved selectivity for sst2 as a result of significant loss of binding affinity at the other ssts. Substitution by DHcy at position 3 in the antagonist scaffold (5), on the other hand, resulted in a significant loss of binding affinity at sst2 and sst3 as compared to the different affinities of the parent compd. (4). The 3D NMR structures of the analogs in dimethylsulfoxide are consistent with the obsd. binding affinities.
