Cyclic side-chain-linked opioid analogs utilizing cis- and trans-4-aminocyclohexyl-d-alanine
作者： Justyna Piekielna , Luca Gentilucci , Rossella De Marco , Renata Perlikowska , Anna Adamska
DOI: 10.1016/J.BMC.2014.10.022
关键词:
摘要: Cyclization of linear sequences is a well recognized tool in opioid peptide chemistry for generating analogs with improved bioactivities. can be achieved through various bridging bonds between ends or side-chains. In our earlier paper we have reported the synthesis and biological activity cyclic peptide, Tyr-c[ d -Lys-Phe-Phe-Asp]NH 2 ( 1 ), which viewed as an analog endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH ). was amide bond side-chains -Lys Asp residues. Here, to increase rigidity structure, replaced cis - trans -4-aminocyclohexyl- -alanine -ACAla). Two sets incorporating either Tyr Dmt (2′,6′-dimethyltyrosine) residues position were synthesized. binding studies -ACAla showed high affinity both, μ- δ-opioid receptors (MOR DOR, respectively) moderate κ-opioid receptor (KOR), while exceptionally MOR-selective. Conformational analyses by NMR molecular docking been performed investigate structural features responsible noteworthy MOR selectivity.
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