Lysine and Arginine Reactivity and Transformation Products during Peptide Chlorination
Lysine and Arginine Reactivity and Transformation Products during Peptide Chlorination
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肽氯化过程中赖氨酸和精氨酸的反应性和转化产物
DOI：
10.1021/acs.est.2c09556
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发表时间：
2023
影响因子：
11.4
通讯作者：
Mitch, William A.
中科院分区：
文献类型：
--
作者：
Shi, Jiaming Lily;Mitch, William A.
氯与肽结合的氨基酸反应形成消毒副产物，并通过降解蛋白质结构和功能来促进病原体灭活。肽结合赖氨酸和精氨酸是七种氯反应性氨基酸中的两种，但它们与氯的反应特征不明显。本研究使用n -乙酰化赖氨酸和精氨酸作为肽结合氨基酸和真实小肽的模型，证明赖氨酸侧链在≤0.5小时内转化为单氯胺和二氯胺，精氨酸侧链转化为单氯胺、二氯胺和三氯胺。赖氨酸氯胺在1周内以6%的产率形成赖氨酸腈和赖氨酸醛。精氨酸氯胺在约1周内以约3%的产率生成鸟氨酸腈，但不生成相应的醛。虽然研究人员假设在氯化过程中观察到的蛋白质聚集是由赖氨酸醛和赖氨酸在不同蛋白质上的共价席夫碱交联引起的，但没有观察到席夫碱形成的证据。氯胺的快速形成和缓慢衰变表明，在与饮用水分布相关的时间尺度上，它们比醛类和腈类与副产物的形成和病原体的失活更相关。以往的研究表明，赖氨酸氯胺对人体细胞具有细胞毒性和遗传毒性。赖氨酸和精氨酸阳离子侧链转化为中性氯胺会改变蛋白质的结构和功能，并通过疏水相互作用增强蛋白质聚集，有助于病原体的失活。
Chlorine reactions with peptide-bound amino acids form disinfection byproducts and contribute to pathogen inactivation by degrading protein structure and function. Peptide-bound lysine and arginine are two of the seven chlorine-reactive amino acids, but their reactions with chlorine are poorly characterized. UsingN-acetylated lysine and arginine as models for peptide-bound amino acids and authentic small peptides, this study demonstrated conversion of the lysine side chain to mono- and dichloramines and the arginine side chain to mono-, di-, and trichloramines in ≤0.5 h. The lysine chloramines formed lysine nitrile and lysine aldehyde at ∼6% yield over ∼1 week. The arginine chloramines formed ornithine nitrile at ∼3% yield over ∼1 week but not the corresponding aldehyde. While researchers hypothesized that the protein aggregation observed during chlorination arises from covalent Schiff base cross-links between lysine aldehyde and lysine on different proteins, no evidence for Schiff base formation was observed. The rapid formation of chloramines and their slow decay indicate that they are more relevant than the aldehydes and nitriles to byproduct formation and pathogen inactivation over timescales relevant to drinking water distribution. Previous research has indicated that lysine chloramines are cytotoxic and genotoxic to human cells. The conversion of lysine and arginine cationic side chains to neutral chloramines should alter protein structure and function and enhance protein aggregation by hydrophobic interactions, contributing to pathogen inactivation.