首页> 外文期刊>Drug design and discovery >Pharmacophore/receptor models for GABA(A)/BzR alpha2beta3gamma2, alpha3beta3gamma2 and alpha4beta3gamma2 recombinant subtypes. Included volume analysis and comparison to alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2 subtypes.
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Pharmacophore/receptor models for GABA(A)/BzR alpha2beta3gamma2, alpha3beta3gamma2 and alpha4beta3gamma2 recombinant subtypes. Included volume analysis and comparison to alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2 subtypes.

机译:GABA(A)/ BzR alpha2beta3gamma2,alpha3beta3gamma2和alpha4beta3gamma2重组亚型的药理学/受体模型。包括体积分析和与alpha1beta3gamma2,alpha5beta3gamma2和alpha6beta3gamma2亚型的比较。

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摘要

Pharmacophore/receptor models for 6 recombinant GABA(A)/BzR subtypes (alphax beta3gamma2, x = 1-6) have been established via an SAR ligand mapping approach. This study was based on the affinities of 166 BzR ligands at 6 distinct (alpha1-6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least twelve different structural families. Examination of the included volumes indicated that the shapes of binding pockets for alpha1, alpha2 and alpha3 subtypes are very similar to each other. Region L2 for the alpha5 containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other subtypes. Moreover, region L3 in the alpha6 subtype is either very small or nonexistent in this diazepam insensitive "DI" subtype as compared to the other subtypes. Preliminary results for the alpha4-containing receptor subtype (DI) indicate that L3 in the alpha4 subtype suffers a similar fate. Use of the pharmacophore/receptor models for these subtypes have resulted in the design of novel BzR ligands selective for the alpha5beta3gamma2, receptor subtype.
机译:通过SAR配体作图方法,已经建立了6种重组GABA(A)/ BzR亚型(alphax beta3gamma2,x = 1-6)的药理学/受体模型。这项研究基于166 BzR配体在来自至少十二个不同结构家族的6种不同(alpha1-6beta3gamma2)重组GABA(A)/ BzR受体亚型的亲和力。检查所包含的体积表明,alpha1,alpha2和alpha3亚型的结合袋的形状彼此非常相似。含α5亚型的区域L2似乎比其他受体亚型的类似区域更大。相反,区域L(Di)在alpha1子类型中似乎比其他子类型大。而且,与其他亚型相比,在这种对地西epa不敏感的“ DI”亚型中,α6亚型中的区域L3非常小或不存在。含alpha4的受体亚型(DI)的初步结果表明,alpha4亚型中的L3受同样的命运。这些亚型的药效基团/受体模型的使用已导致对α5beta3gamma2受体亚型具有选择性的新型BzR配体的设计。

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