New sst4/5-selective somatostatin peptidomimetics based on a constrained tryptophan scaffold.
The synthesis and biological evaluation of four peptidomimetic analogs of somatostatin based on a constrained Trp residue, 3-amino-indolo[2,3-c]azepin-2-one (Aia), are reported. It is shown that dipeptidomimetics with a D-Aia-Lys sequence, functionalized with N- and C-terminal aromatic substituents, display a good selectivity for both sst4 and sst5. This study allowed us to identify a new highly potent sst5 agonist with good selectivity over the other receptors, except versus sst4.
Feytens
Debby
D
Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium.
Cescato
Renzo
R
Reubi
Jean Claude
JC
Tourwé
Dirk
D
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D008968:Molecular Conformation; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D013004:Somatostatin / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry*
D013004:Somatostatin; D014364:Tryptophan; D000242:Cyclic AMP