Optimization of a somatostatin mimetic via constrained amino acid and backbone incorporation.
Constrained analogues 5-7 of the potent and subtype selective somatostatin mimetic 1 were prepared by incorporating conformational constraints into the nine-membered heterocyclic scaffold. Each constrained peptidomimetic showed an altered activity profile relative to lead compound 1, with compound 7 exhibiting a 25-fold and 2-fold binding enhancement against somatostatin receptor subtypes sst4 and sst5, respectively.
Souers
A J
AJ
Department of Chemistry, University of California, Berkeley 94720, USA.
Rosenquist
A
A
Jarvie
E M
EM
Ladlow
M
M
Feniuk
W
W
Ellman
J A
JA
D001667:Binding, Competitive; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D018716:Molecular Mimicry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D017481:Receptors, Somatostatin; D013004:Somatostatin