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New sst4/5-selective somatostatin peptidomimetics based on a constrained tryptophan scaffold
Debby Feytens1, Renzo Cescato, Jean Claude Reubi
1Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium.
Abstract:
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.
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