Lasota Anika, Frączak Oliwia, Leśniak Anna, Muchowska Adriana, Lipkowski Andrzej W, Nowakowski Michał, Ejchart Andrzej, Olma Aleksandra
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Lodz, Poland.
J Pept Sci. 2015 Feb;21(2):120-5. doi: 10.1002/psc.2738. Epub 2014 Dec 30.
New analogues of deltorphin I (DT I, Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 ), with the D-Ala residue in position 2 replaced by α-methyl-β-azido(amino, 1-pyrrolidinyl, 1-piperidinyl or 4-morpholinyl)alanine, were synthesized by a combination of solid-phase and solution methods. All ten new analogues were tested for receptor affinity and selectivity to μ- and δ-opioid receptors. The affinity of analogues containing (R) or (S)-α-methyl-β-azidoalanine in position 2 to δ-receptors strongly depended on the chirality of the α,α-disubstituted residue. Peptide II, containing (S)-α-methyl-β-azidoalanine in position 2, displayed excellent δ-receptor selectivity with its δ-receptor affinity being only three times lower than that of DT I.
采用固相法与溶液法相结合的方式，合成了强啡肽 I（DT I，Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2）的新型类似物，其中第 2 位的 D-Ala 残基被 α-甲基-β-叠氮基（氨基、1-吡咯烷基、1-哌啶基或 4-吗啉基）丙氨酸取代。对所有十种新型类似物进行了 μ-和 δ-阿片受体的受体亲和力和选择性测试。第 2 位含有（R）或（S）-α-甲基-β-叠氮基丙氨酸的类似物对 δ-受体的亲和力强烈依赖于 α,α-二取代残基的手性。第 2 位含有（S）-α-甲基-β-叠氮基丙氨酸的肽 II 表现出优异的 δ-受体选择性——其对 δ-受体的亲和力仅比 DT I 低三倍。
