...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of the American Society for Mass Spectrometry >A novel salt bridge mechanism highlights the need for nonmobile proton conditions to promote disulfide bond cleavage in protonated peptides under low-energy collisional activation
【24h】

A novel salt bridge mechanism highlights the need for nonmobile proton conditions to promote disulfide bond cleavage in protonated peptides under low-energy collisional activation

机译：一种新颖的盐桥机制强调了在低能碰撞活化下非移动质子条件促进质子化肽中二硫键裂解的必要性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The gas-phase fragmentation mechanisms of small models for peptides containing intermolecular disulfide links have been studied using a combination of tandem mass spectrometry experiments, isotopic labeling, Structural labeling, accurate mass measurements of product ions, and theoretical calculations (at the MP2/6-311 + G(2d,p)//B3LYP/3-21G(d) level of theory). Cystine and its C-terminal derivatives were observed to fragment via a range of pathways, including loss of neutral molecules, amide bond cleavage, and S-S and C-S bond cleavages. Various mechanisms were considered to rationalize S-S and C-S bond cleavage processes, including charge directed neighboring group processes and nonmobile proton salt bridge mechanism. Three low-energy fragmentation pathways were identified from theoretical calculations on cystine N-methyl amide: (1) S-S bond cleavage dominated by a neighboring group process involving the C-terminal amide N to form either a protonated cysteine derivative or protonated sulfenyl amide product ion (44.3 kcal mol(-1)); (2) C-S bond cleavage via a salt bridge mechanism, involving abstraction of the alpha-hydrogen by the N-terminal amino group to form a protonated thiocysteine derivative (35.0 kcal mol(-1)); and (3) C-S bond cleavage via a Crob-like fragmentation process in which the nucleophilic N-terminal amino group forms a protonated dithiazolidine (57.9 kcal mol(-1)). Interestingly, C-S bond cleavage by neighboring group processes have high activation barriers (63.1 kcal mol(-1)) and are thus not expected to be accessible during low-energy CID experiments. If) comparison to the energetics of simple amide bond cleavage, these S-S and C-S bond cleavage reactions are higher in energy, which helps rationalize why bond cleavage processes involving the disulfide bond are rarely observed for low-energy CID of peptides with mobile proton(s) containing intermolecular disulfide bonds. On the other hand, the absence of a mobile proton appears to "switch on" disulfide bond cleavage reactions, which can be rationalized by the salt bridge mechanism. This potentially has important ramifications in explaining the prevalence of disulfide bond cleavage in singly protonated peptides under MALDI conditions.
机译：结合串联质谱实验，同位素标记，结构标记，精确的产物离子质量测量和理论计算（在MP2 / 6-上），已经研究了小模型包含分子间二硫键的肽的气相裂解机理。 311 + G（2d，p）// B3LYP / 3-21G（d）理论水平）。观察到胱氨酸及其C端衍生物通过一系列途径断裂，包括中性分子的丢失，酰胺键的裂解以及S-S和C-S键的裂解。人们考虑了各种机制来合理化S-S和C-S键的裂解过程，包括电荷定向的邻近基团过程和非移动质子盐桥机制。从对胱氨酸N-甲基酰胺的理论计算中确定了三种低能裂解途径：（1）SS键断裂由涉及C端酰胺N的邻基过程主导，形成质子化的半胱氨酸衍生物或质子化的亚磺酰胺产物离子（44.3 kcal mol（-1））; （2）通过盐桥机制裂解C-S键，涉及通过N端氨基抽象化α-氢以形成质子化的硫代半胱氨酸衍生物（35.0 kcal mol（-1））; （3）通过Crob样断裂过程裂解C-S键，其中亲核N末端氨基形成质子化的二噻唑烷（57.9 kcal mol（-1））。有趣的是，通过邻近基团过程进行的C-S键裂解具有较高的激活势垒（63.1 kcal mol（-1）），因此在低能CID实验中无法预期可及。如果与简单酰胺键裂解的能量学相比，这些SS和CS键裂解反应的能量更高，这有助于合理化为什么很少观察到带有移动质子的肽的低能CID涉及二硫键的裂解过程）含有分子间二硫键。另一方面，不存在可移动的质子似乎“开启”了二硫键裂解反应，这可以通过盐桥机制来合理化。这可能对解释在MALDI条件下单质子化的肽中二硫键裂解的普遍性具有重要意义。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号