Department of Chemistry, School of Chemical Sciences, Central University of Karnataka, Kalaburagi, Karnataka, India.
Solid State and Structural Chemistry Unit (SSCU), Indian Institute of Science, Bangalore, Karnataka, India.
J Pept Sci. 2020 Apr;26(4-5):e3245. doi: 10.1002/psc.3245. Epub 2020 Feb 26.
Conformations of disulfide and diselenide were compared in (Boc-Cys/Sec-NHMe) and (Boc-Cys/Sec-OMe) using X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, density functional theory (DFT), and circular dichroism (CD) spectroscopy. Conformations of disulfide/diselenide in polypeptides are defined based on the sign of side chain torsion angle χ (-CH -S/Se-S/Se-CH -); negative indicates left-handed and positive indicates right-handed orientation. In the crystals of (Boc-Cys-OMe) and (Boc-Sec-OMe) , the disulfide exhibits a left-handed and the diselenide a right-handed orientation. Characterization of cystine and selenocystine derivatives in solution using H-NMR, natural abundant Se NMR, 2D-ROESY, and chemical shift analysis coupled to DMSO titration has indicated the symmetrical nature and antiparallel orientation of Cys/Sec residues about the disulfide/diselenide bridges. Structural calculations of cystine and selenocystine derivatives using DFT further support the antiparallel orientation of Cys/Sec residues about disulfide/diselenide. The far-ultraviolet (UV) region CD spectra of cystine and selenocystine derivatives have exhibited the negative Cotton effect (CE) for disulfide and positive for diselenide confirming the difference in the conformational preference of disulfide and diselenide. In the previously reported polymorphic structure of (Boc-Sec-OMe) , the diselenide has right-handed orientation. In the X-ray structures of disulfide and diselenide analogues of Escherichia coli protein encoded by curli specific gene C (CgsC) retrieved from Protein Databank (PDB), disulfide has left-handed and the diselenide right-handed orientation. The current report provides the evidence for the local conformational difference between a disulfide and a diselenide group under unconstrained conditions, which may be useful for the rational replacement of disulfide by diselenide in polypeptide chains.
采用 X 射线晶体学、核磁共振（NMR）光谱学、密度泛函理论（DFT）和圆二色性（CD）光谱学比较了 Boc-Cys/Sec-NHMe 和 Boc-Cys/Sec-OMe 中二硫键和硒代二硫键的构象。多肽中二硫键/硒代二硫键的构象基于侧链扭转角 χ（-CH-S/Se-S/Se-CH-）的符号来定义；负号表示左手，正号表示右手取向。在 Boc-Cys-OMe 和 Boc-Sec-OMe 的晶体中，二硫键呈现左手，硒代二硫键呈现右手取向。使用 1H-NMR、天然丰度 77Se-NMR、2D-ROESY 和化学位移分析结合 DMSO 滴定对胱氨酸和硒代胱氨酸衍生物在溶液中的特性进行了表征，表明 Cys/Se 残基在二硫键/硒代二硫键桥处具有对称性质和反平行取向。使用 DFT 对胱氨酸和硒代胱氨酸衍生物的结构计算进一步支持 Cys/Se 残基在二硫键/硒代二硫键处的反平行取向。胱氨酸和硒代胱氨酸衍生物的远紫外（UV）区 CD 光谱表现出二硫键的负 Cotton 效应（CE）和硒代二硫键的正 CE，证实了二硫键和硒代二硫键在构象偏好上的差异。在先前报道的 Boc-Sec-OMe 多晶型结构中，硒代二硫键呈现右手取向。从蛋白质数据库（PDB）中检索到的大肠杆菌卷曲特定基因 C（CgsC）编码的蛋白质中二硫键和硒代二硫键类似物的 X 射线结构中，二硫键呈现左手，硒代二硫键呈现右手取向。本报告提供了在不受约束条件下二硫键和硒代二硫键基团之间局部构象差异的证据，这对于在多肽链中合理地用硒代二硫键替代二硫键可能是有用的。
