Effect of Hydrogen Bonding and Partial Deprotonation on the Oxidation of Peptides
Effect of Hydrogen Bonding and Partial Deprotonation on the Oxidation of Peptides
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氢键和部分去质子化对肽氧化的影响
DOI：
10.1021/acs.jpca.7b11797
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
L.
中科院分区：
文献类型：
--
作者：
Chan;B.; Easton;C. J.; Radom;L.
在最近的一项计算研究中，我们发现氢键/部分去质子化促进了随后的电子从酰胺到HO·的转移。我们现在已经用甘氨酸衍生物作为模型肽分析了这些反应和相关反应，不仅研究了反应能量，还研究了各个步骤的障碍。我们发现，部分去质子化不仅有助于后续的电子转移(一种顺序质子损失电子转移(SPLET)类型的反应途径)，而且还促进顺序氢原子转移(HAT，在顺序质子损失氢原子转移(SPLHAT)类型的过程中)，两者都是作为多肽氧化的直接HAT的潜在替代途径。这些替代路径中的每一条都被计算为具有可访问性和竞争力的能源需求。这些氧化过程可能会产生以α为中心的多肽自由基，通过去质子化，很容易被氧化成相应的亚胺。我们还通过比较甘氨酸模型和类似的缬氨酸衍生物的反应，研究了氨基酸侧链竞争反应的可能性。我们发现，虽然氨基酸的侧链对直接HAT更具反应性，但之前的部分去质子化反应继续有利于SPLET和SPLHAT-型反应，导致α-碳中心肽自由基的产生。综上所述，这些过程具有广泛的影响，影响了多肽的科学和效用的许多方面。
In a recent computational study, we found that hydrogen bonding/partial deprotonation facilitates subsequent electron transfer from amides to HO•. We have now analyzed these and related reactions with a glycine derivative as a model peptide, investigating not only reaction energies but also barriers for the individual steps. We find that partial deprotonation not only assists subsequent electron transfer (a sequential proton-loss electron-transfer (SPLET)-type reaction pathway) but also promotes sequential hydrogen-atom transfer (HAT, in a sequential proton-loss hydrogen-atom-transfer (SPLHAT)-type process), both being potential alternatives to direct HAT as routes for peptide oxidation. Each of these alternative pathways is calculated to have energy requirements that make them accessible and competitive. These oxidative processes may produce α-carbon-centered peptide radicals that, through deprotonation, are readily oxidized to the corresponding imines. We have also examined the possibility of competing reactions of amino acid side chains by comparing reactions of the glycine model with those of an analogous valine derivative. We find that, while the side chains of amino acids are more reactive toward direct HAT, a preceding partial deprotonation instead continues to favor the SPLET- and SPLHAT-type reactions, leading to the production of α-carbon-centered peptide radicals. Taken together, these processes have broad implications that impact many aspects of the science and utility of peptides.