Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4'-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors.
Verifying the role of 3-hydroxy of 17-cyclopropylmethyl-4,5α-epoxy-3,14β-dihydroxy-6β-[(4'-pyridyl) carboxamido]morphinan derivatives via their binding affinity and selectivity profiles on opioid receptors.
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DOI：
10.1016/j.bioorg.2021.104702
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发表时间：
2021-04
影响因子：
5.1
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Huang B;Gunta R;Wang H;Li M;Cao D;Mendez RE;Gillespie JC;Chen C;Huang LM;Liu-Chen LY;Selley DE;Zhang Y
本文研究了一系列环氧吗啡喃衍生物的3-羟基在其与阿片受体结合亲和力和选择性中的作用。发现3-羟基对于这些衍生物对所有三种OR的结合亲和力是至关重要的，因为所有类似物1a-e与其对应物3-脱羟基酮6a-e相比表现出显著更高的结合亲和力。同时，大多数携带3-羟基的化合物具有类似的选择性概况的κ阿片受体的μ阿片受体作为其相应的3-脱羟基衍生物。[35 S]-GTPγS功能测定结果表明，这些环氧吗啡喃衍生物的3-羟基对于维持其对OR的效力具有重要作用，并具有不同的作用。进一步的分子模拟研究有助于理解化合物1c（NCP）及其3-脱羟基类似物6c之间显着不同的结合亲和力和功能概况。
In the present study, the role of 3-hydroxy group of a series of epoxymorphinan derivatives in their binding affinity and selectivity profiles toward the opioid receptors (ORs) has been investigated. It was found that the 3-hydroxy group was crucial for the binding affinity of these derivatives for all three ORs due to the fact that all the analogues 1a-e exhibited significantly higher binding affinities compared to their counterpart 3-dehydroxy ones 6a-e. Meanwhile most compounds carrying the 3-hydroxy group possessed similar selectivity profiles for the kappa opioid receptor over the mu opioid receptor as their corresponding 3-dehydroxy derivatives. [35S]-GTPγS functional assay results indicated that the 3-hydroxy group of these epoxymorphinan derivatives was important for maintaining their potency on the ORs with various effects. Further molecular modeling studies helped comprehend the remarkably different binding affinity and functional profiles between compound 1c (NCP) and its 3-dehydroxy analogue 6c.
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影响因子：
64.8
作者：
Huang W;Manglik A;Venkatakrishnan AJ;Laeremans T;Feinberg EN;Sanborn AL;Kato HE;Livingston KE;Thorsen TS;Kling RC;Granier S;Gmeiner P;Husbands SM;Traynor JR;Weis WI;Steyaert J;Dror RO;Kobilka BK
通讯作者：
Kobilka BK
影响因子：
7.3
作者：
Li G;Aschenbach LC;Chen J;Cassidy MP;Stevens DL;Gabra BH;Selley DE;Dewey WL;Westkaemper RB;Zhang Y
通讯作者：
Zhang Y
影响因子：
64.8
作者：
Granier, Sebastien;Manglik, Aashish;Kruse, Andrew C.;Kobilka, Tong Sun;Thian, Foon Sun;Weis, William I.;Kobilka, Brian K.
通讯作者：
Kobilka, Brian K.
影响因子：
5.6
作者：
Jones, G;Willett, P;Taylor, R
通讯作者：
Taylor, R
影响因子：
2.7
作者：
Li, Guo;Aschenbach, Lindsey C. K.;Zhang, Yan
通讯作者：
Zhang, Yan