气相离子中肽和腈胺立体化学上不同支架的光化学和碰撞诱导交联。

IF 3.1 2区 化学 Q2 BIOCHEMICAL RESEARCH METHODS
Hongyi Zhu, Marianna Nytka, Tuan Ngoc Kim Vu, Karel Lemr, František Tureček
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引用次数: 0

摘要

在立体化学性质不同的共轭物中研究了肽与腈-亚胺中间体之间的分子内交联,其中反应组分分别安装在顺式-1,2-环己烷和反式-1,4-环己烷支架上,我们分别称之为 1,2-s 肽和 1,4-s 肽。腈-亚胺中间体是在 213 纳米和 250 纳米紫外光解离或碰撞诱导解离时从 2,5-二叔四氮唑标签中失去 N2 而生成的,并通过 CID 和 UVPD-MS3 进行了进一步检测。区分了来自线性结构和大环交联的肽片段离子系列,并用于量化交联产率。根据肽序列的不同,MS2 的产率从 AAAG 共轭物的 27% 到 GAAAK 共轭物的 78% 不等。根据肽序列的不同,CID-MS3 收率在 57% 到 97% 之间。通过高分辨率循环离子迁移率,并结合玻恩-奥本海默分子动力学和密度泛函理论计算,研究了 1,2-s 肽和 1,4-s 肽离子的结构及其腈-亚胺中间体和交联物。实验与计算的碰撞截面和离子相对吉布斯能之间的匹配被用来确定肽的结构。通过 MS3 测序确定了以甘氨酸和赖氨酸残基为 C 端的多肽共轭物发生了羧基交联,降低交联产率的羧基阻断实验也证实了这一点。以 Arg 为 C 端的多肽共轭物也通过侧链胍基交联。1,4-s-肽离子的一个显著特点是低能捻船环己烷构象的参与,这是由肽和腈亚胺之间的强氢键促成的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Photochemical and Collision-Induced Cross-Linking in Stereochemically Distinct Scaffolds of Peptides and Nitrile Imines in Gas-Phase Ions.

Intramolecular cross-linking between peptides and nitrile-imine intermediates was studied in stereochemically distinct conjugates in which the reacting components were mounted on cis-1,2-cyclohexane and trans-1,4-cyclohexane scaffolds that we call 1,2-s-peptides and 1,4-s-peptides, respectively. The nitrile-imine intermediates were generated by N2 loss from 2,5-diaryltetrazole tags upon UV-photodissociation at 213 and 250 nm or by collision-induced dissociation, and further interrogated by CID and UVPD-MS3. Peptide fragment ion series originating from linear structures and macrocyclic cross-links were distinguished and used to quantify the cross-linking yields. The yields in MS2 varied between 27% for AAAG conjugates to 78% for GAAAK conjugates, depending on the peptide sequence. The CID-MS3 yields were in a 57-97% range, depending on the peptide sequence. Structures of 1,2-s-peptide and 1,4-s-peptide ions as well as several of their nitrile-imine intermediates and cross-links were investigated by high-resolution cyclic ion mobility in combination with Born-Oppenheimer molecular dynamics and density functional theory calculations. Matches between the experimental and calculated collision cross sections and ion relative Gibbs energies were used to assign peptide structures. Peptide conjugates C-terminated with Gly and Lys residues underwent cross-linking by the carboxyl group, as established by MS3 sequencing and corroborated by carboxyl blocking experiments that lowered the cross-linking yields. Peptide conjugates C-terminated with Arg also cross-linked via the side-chain guanidine group. A notable feature of the 1,4-s-peptide ions was the participation of low-energy twist-boat cyclohexane conformers that was enforced by strong hydrogen bonds between the peptide and nitrile imine.

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来源期刊
CiteScore
5.50
自引率
9.40%
发文量
257
审稿时长
1 months
期刊介绍: The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role. Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives
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