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短部分肽对肾上腺素能受体的分子识别:一种自下而上的方法。

Molecular Recognition by a Short Partial Peptide of the Adrenergic Receptor: A Bottom-Up Approach.

机构信息

Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.

School of Life Science and Technology, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.

出版信息

Angew Chem Int Ed Engl. 2018 May 14;57(20):5626-5629. doi: 10.1002/anie.201712976. Epub 2018 Mar 9.

DOI:10.1002/anie.201712976
PMID:29469221
Abstract

Receptor-neurotransmitter molecular recognition is key for neurotransmission. Although crystal structures of the receptors are known, the mechanism for recognition is not clear. Reported here is the ultraviolet (UV) and infrared (IR) spectra of complexes between a partial peptide (SIVSF), mimicking the binding motif of a catechol ring in the adrenergic receptor, and various ligands. The UV spectra show that two isomers coexist in the complex of SIVSF with properly recognized ligands, such as protonated adrenaline (adrenalineH ). From IR spectra, they are assigned to catechol- and amino-bound structures. The catechol-bound structure is not observed when the ligand is replaced by nonproper molecules, such as noradrenalineH . The results suggest that SIVSF not only recognizes the catechol ring but can distinguish differences in the amine side chain. The method provides a new possibility for screening molecules as potential therapeutics for activating the receptor.

摘要

受体-神经递质分子识别是神经传递的关键。尽管已经知道受体的晶体结构,但识别机制尚不清楚。本文报道了模拟儿茶酚环在肾上腺素能受体中结合模式的部分肽(SIVSF)与各种配体之间形成的复合物的紫外(UV)和红外(IR)光谱。紫外光谱表明,在 SIVSF 与适当识别的配体(如质子化肾上腺素(adrenalinH ))形成的复合物中存在两种异构体共存。从红外光谱来看,它们被分配到儿茶酚和氨基结合结构。当配体被非适当的分子(如去甲肾上腺素 H )取代时,不会观察到儿茶酚结合结构。结果表明,SIVSF 不仅可以识别儿茶酚环,还可以区分胺侧链的差异。该方法为筛选作为潜在治疗药物激活受体的分子提供了新的可能性。

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