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Inhibition of catechol-O-methyltransferase (COMT) by heparin oligosaccharides with specific structures
Carbohydrate Polymers ( IF 10.7 ) Pub Date : 2024-02-04 , DOI: 10.1016/j.carbpol.2024.121909
Qingqing Chen 1 , Qingchi Wang 2 , Changkai Bu 1 , Zizhe An 1 , Lan Jin 1 , Lianli Chi 1
Carbohydrate Polymers ( IF 10.7 ) Pub Date : 2024-02-04 , DOI: 10.1016/j.carbpol.2024.121909
Qingqing Chen 1 , Qingchi Wang 2 , Changkai Bu 1 , Zizhe An 1 , Lan Jin 1 , Lianli Chi 1
Affiliation
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COMT inhibitors are commonly used to improve the effectiveness of levodopa in treating Parkinson's disease by inhibiting its conversion to 3--methyldopa. Because of the serious side effect of nitrocatechol COMT inhibitors, it is necessary to develop non-nitrocatechol COMT inhibitors with a higher safety profile. Heparin has been observed to bind to COMT. However, the exact functional significance of this interaction is not fully understood. In this study, the contribution of different substitution of heparin to its binding with COMT was investigated. and , heparin oligosaccharides can bind to COMT and inhibit its activity. Furthermore, we enriched the functional heparin oligosaccharides that bind to COMT and identified the sequence UA2S-GlcN(S/Ac)6(S/H)-UA2S-GlcNS6(S/H)-UA2(S/H)-GlcNS6S as the characteristic structural domain of these functional oligosaccharides. This study has elucidated the relationship between the structure of heparin oligosaccharides and their activity against COMT, providing valuable insights for the development of non-nitrocatechol COMT inhibitors with improved safety and efficacy.
中文翻译：
特定结构的肝素寡糖对儿茶酚-O-甲基转移酶（COMT）的抑制作用
COMT抑制剂通常用于通过抑制左旋多巴转化为3-甲基多巴来提高左旋多巴治疗帕金森病的有效性。由于硝基儿茶酚COMT抑制剂具有严重的副作用，因此有必要开发安全性更高的非硝基儿茶酚COMT抑制剂。已观察到肝素与 COMT 结合。然而，这种相互作用的确切功能意义尚不完全清楚。在本研究中，研究了肝素的不同取代对其与 COMT 结合的贡献。并且，肝素寡糖可以与 COMT 结合并抑制其活性。此外，我们还富集了与COMT结合的功能性肝素寡糖，并鉴定了序列UA2S-GlcN(S/Ac)6(S/H)-UA2S-GlcNS6(S/H)-UA2(S/H)-GlcNS6S作为这些功能性寡糖的特征结构域。本研究阐明了肝素寡糖的结构与其抗 COMT 活性之间的关系，为开发安全性和有效性更高的非硝基儿茶酚 COMT 抑制剂提供了宝贵的见解。
更新日期：2024-02-04
中文翻译：
特定结构的肝素寡糖对儿茶酚-O-甲基转移酶（COMT）的抑制作用
COMT抑制剂通常用于通过抑制左旋多巴转化为3-甲基多巴来提高左旋多巴治疗帕金森病的有效性。由于硝基儿茶酚COMT抑制剂具有严重的副作用，因此有必要开发安全性更高的非硝基儿茶酚COMT抑制剂。已观察到肝素与 COMT 结合。然而，这种相互作用的确切功能意义尚不完全清楚。在本研究中，研究了肝素的不同取代对其与 COMT 结合的贡献。并且，肝素寡糖可以与 COMT 结合并抑制其活性。此外，我们还富集了与COMT结合的功能性肝素寡糖，并鉴定了序列UA2S-GlcN(S/Ac)6(S/H)-UA2S-GlcNS6(S/H)-UA2(S/H)-GlcNS6S作为这些功能性寡糖的特征结构域。本研究阐明了肝素寡糖的结构与其抗 COMT 活性之间的关系，为开发安全性和有效性更高的非硝基儿茶酚 COMT 抑制剂提供了宝贵的见解。
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