Degradation of hyaluronic acid, poly- and monosaccharides and model compounds by hypochlorite: Evidence for radical intermediates and fragmentation
Degradation of hyaluronic acid, poly- and monosaccharides and model compounds by hypochlorite: Evidence for radical intermediates and fragmentation
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DOI：
10.1016/s0891-5849(98)00009-4
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发表时间：
1998-06-01
影响因子：
7.4
通讯作者：
Davies, MJ
中科院分区：
文献类型：
--
作者：
Hawkins, CL;Davies, MJ
透明质酸被氧化剂如HO降解。和HOCl/ClO-被认为在类风湿关节炎的进展中很重要。透明质酸与HO的反应。虽然已被广泛研究，但与HOCl/ClO-的反应不太明确。因此，对于HOCl/ClO-攻击的位置，中间体形成的位置知之甚少。或者聚合物降解的机制。本研究利用紫外可见光谱（220-340 nm）和EPR光谱对HOCl/ClO-与酰胺、糖、多糖和透明质酸的反应进行了监测。紫外可见实验表明，HOCl/ClO-优先与n -乙酰基反应。该反应被认为产生瞬时氯酰胺（R-NCl-C(O)-R′），这些物质通过均解(产生N。和Cl .)或异解音电子还原，得到N-Cl键的N和Cl-)。用EPR自旋俘获法研究了形成的自由基的性质。HOCl/ClO-与透明质酸、硫酸软骨素A和C、n-乙酰糖和酰胺的反应产生了新的碳中心自旋加合物，其形成与n-乙酰基的选择性初始攻击一致。因此，与透明质酸和硫酸软骨素A的反应，似乎局限于n -乙酰氨基葡萄糖糖环。这些以碳为中心的自由基被认为是由n-乙酰氯酰胺形成的初始氮为中心的自由基通过与烷氧基自由基类似的反应迅速重排而产生的。随着HOCl/ClO-浓度的增加，透明质酸和硫酸软骨素A的低分子量自由基加合物的产率增加，这表明n-乙酰氨基葡萄糖环上初始氮中心自由基的形成以及由此衍生的碳中心自由基导致了聚合物的断裂。(C) 1998爱思唯尔科学有限公司
Degradation of hyaluronic acid by oxidants such as HO. and HOCl/ClO- is believed to be important in the progression of rheumatoid arthritis. While reaction of hyaluronic acid with HO. has been investigated extensively, reaction with HOCl/ClO- is less well defined. Thus, little is known about the site(s) of HOCl/ClO- attack, the intermediates formed. or the mechanism(s) of polymer degradation. In this study reaction of HOCl/ClO- with amides, sugars, polysaccharides, and hyaluronic acid has been monitored by UV-visible (220-340 nm) and EPR spectroscopy. UV-visible experiments have shown that HOCl/ClO- reacts preferentially with N-acetyl groups. This reaction is believed to give rise to transient chloramide (R-NCl-C(O)-R') species, which decompose rapidly to give radicals via either homolysis (to produce N . and Cl .) or heterolysis tone-electron reduction, to give N and Cl-) of the N-Cl bond. The nature of the radicals formed has been investigated by EPR spin trapping. Reaction of HOCl/ClO- with hyaluronic acid, chondroitin sulphates A and C, N-acetyl sugars, and amides gave novel, carbon-centered, spin adducts, the formation of which is consistent with selective initial attack at the N-acetyl group. Thus, reaction with hyaluronic acid and chondroitin sulphate A, appears to be localized at the N-acetylglucosamine sugar rings. These carbon-centered radicals are suggested to arise from rapid rearrangement of initial nitrogen-centered radicals, formed from the N-acetyl chloramide, by reactions analogous to those observed with alkoxyl radicals. The detection of increasing yields of low-molecular-weight radical adducts from hyaluronic acid and chondroitin sulphate A with increasing HOCl/ClO- concentrations suggests that formation of the initial nitrogen-centered species on the N-acetylglucosamine rings, and the carbon-centered radicals derived from them, brings about polymer fragmentation. (C) 1998 Elsevier Science Inc.