Molecular Recognition by a Short Partial Peptide of the Adrenergic Receptor: A Bottom-Up Approach
Molecular Recognition by a Short Partial Peptide of the Adrenergic Receptor: A Bottom-Up Approach
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肾上腺素受体短部分肽的分子识别：自下而上的方法
DOI：
10.1002/anie.201712976
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
M. Fujii
中科院分区：
文献类型：
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作者：
T. Sekiguchi;M. Tamura;H. Oba;P. Carcarbal;R. R. Lozada-Garcia;A. Zehnacker-Rentien;G. Gregoire;S. Ishiuchi;M. Fujii
受体-神经递质分子识别是神经传递的关键。虽然受体的晶体结构是已知的，但识别机制尚不清楚。本文报道了模拟肾上腺素能受体中儿茶酚环结合基序的部分肽（SIVSF）和各种配体之间复合物的紫外（UV）和红外（IR）光谱。紫外光谱表明，两种异构体共存的SIVSF与适当识别的配体，如质子化肾上腺素（adrenalineH+）的复合物。根据IR光谱，它们被归属于邻苯二酚和氨基结合的结构。当配体被不合适的分子（如去甲肾上腺素H+）取代时，未观察到儿茶酚结合结构。结果表明，SIVSF不仅识别邻苯二酚环，但可以区分胺侧链的差异。该方法为筛选作为激活受体的潜在治疗剂的分子提供了新的可能性。
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.