Dithiolated peptides incorporating bis(tryptophan)s for cooperative mercury(II) binding
Dithiolated peptides incorporating bis(tryptophan)s for cooperative mercury(II) binding
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掺入双（色氨酸）的二硫醇化肽可协同结合汞（II）
DOI：
10.1016/j.bmc.2021.116296
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发表时间：
2021
影响因子：
3.5
通讯作者：
Todd, Daniel
中科院分区：
文献类型：
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作者：
Ngu-Schwemlein, Maria;Merle, John;Cameron, T'ea;Witcher, Charlexia;Todd, Daniel
色氨酸的吲哚侧链是一种多功能的π-供体，可以参与各种类型的阳离子-π相互作用。了解它是如何作为辅助结合基团在汞（II）络合物中发挥作用的，可以为设计有效的螯合剂以实现最佳的汞固定提供有价值的见解。在这项研究中，我们调查如何纳入两个色氨酸残基模型双半胱氨酸肽可能参与肽汞（II）复合物的稳定。设计了两个由Cys-Trp-Cys序列基序组成的五肽，其中在N-末端（BT 1）或C-末端（BT 2）含有第二个色氨酸残基。包括一个类似的环己肽（BT3），以评估如何色氨酸残基，限制在受约束的肽转基序，可能会参加汞（II）络合。它们与汞（II）的相互作用进行了研究，通过光谱方法和计算模型。UV-vis研究表明形成了1：1的二硫代汞（II）络合物，这通过ESI-MS分析得到证实。光谱研究表明，BT 1和BT 3中的色氨酸吲哚基团可以参与汞离子与π的相互作用。优化的1：1汞（II）-BT3结构表明，两个吲哚环都非常靠近汞（II）配位，可以通过屏蔽配体交换来稳定汞（II）配位。这些发现提供了一些有用的见解，对使用芳香族供体基团作为疏水屏蔽在设计更有效的金属螯合剂。
The indole side chain of tryptophan is a versatile π-donor that can participate in various types of cation-π interactions. An understanding of how it may contribute as an auxiliary binding group in mercury(II) complexes can provide valuable insights toward the design of effective chelators for optimal mercury immobilization. In this study, we investigate how the incorporation of two tryptophan residues in model dicysteinyl peptides might participate in peptide-mercury(II) complex stabilization. Two pentapeptides consisting of a Cys-Trp-Cys sequence motif containing a second tryptophan residue at theN-terminal (BT1) or C-terminal (BT2) were designed. An analogous cyclohexapeptide (BT3) was included to evaluate how tryptophan residues, restricted in constrained peptidic turn motifs, might take part in mercury(II) complexation. Their interactions with mercury(II) were investigated by spectroscopic methods and computational modeling. UV–vis studies indicate the formation of 1:1 dithiolated mercury(II) complex, which is corroborated by ESI-MS analysis. Spectroscopic studies reveal that the tryptophan indole group(s) inBT1andBT3can participate in mercury(II) cation-π interactions. Optimized 1:1 mercury(II)-BT3structures indicate that both indole rings are very close to the mercury(II) coordination site and could stabilize it by shielding it from ligand exchange. These findings provide some useful insights toward use of aromatic donor groups as hydrophobic shields in designing more effective metal chelating agents.