通过保罗酸的加成提高保罗霉素的稳定性
收稿日期: 2018-05-28
修回日期: 2018-06-22
网络出版日期: 2018-07-05
基金资助
国家自然科学基金（No.31670032和31522001）资助项目.
Improvement of Paulomycin Stability by Addition of Paulic Acid
Received date: 2018-05-28
Revised date: 2018-06-22
Online published: 2018-07-05
Supported by
Project supported by the National Natural Science Foundation of China (No. 31670032 & 31522001).
保罗霉素（paulomycin）是由链霉菌产生的糖苷类抗生素，不仅对革兰氏阳性细菌有很好的抗菌活性，也具有良好的抗肿瘤活性.其结构中保罗酸基团是造成该类化合物不稳定的主要原因之一.本研究旨在提高保罗霉素的稳定性.通过向保罗霉素产生菌的发酵液中添加小分子硫醇类化合物N-乙酰半胱胺（SNAC），经发酵分离及结构解析，获得了新结构的保罗霉素衍生物palsimycins A、B、C、D.抗菌活性实验表明，palsimycin A、palsimycin B对测试菌株的最小抑菌浓度（MIC）与paulomycin A、paulomycin B的MIC值处于同一水平.酸碱稳定性实验揭示，相同条件下，palsimycins A、B、C、D均比paulomycin A、paulomycin B更加稳定.因此，在不影响抗菌活性的前提下，本研究通过保罗酸部位的加成，提高了保罗霉素的稳定性，为该类化合物的进一步应用研究奠定了基础.
唐越 , 王敏 , 丁勇 , 李金娥 , 陈义华 . 通过保罗酸的加成提高保罗霉素的稳定性[J]. 有机化学, 2018 , 38(9) : 2420 -2426 . DOI: 10.6023/cjoc201805045
Paulomycins are a group glycoside antibiotics produced by Streptomyces, which not only show excellent antibacterial activities against gram-positive bacteria, but also display good antitumor activities. The paulic acid moiety is one of the structures that cause the instability of paulomycin. This study aimed to improve the stability of paulomycins. When small molecule thiol compound N-acetylcysteamine (SNAC) was added to the fermentation broth of paulmycin producing strain, four new paulomycin derivatives of palsimycins A, B, C, and D were obtained. The antibacterial activity evaluation showed that the minimal inhibit concentrations (MICs) of palsimycin A and palsimycin B against the tested strains were at the same level as those of paulomycin A and paulomycin B. The stability test revealed that under the same conditions, palsimycin A, B, C, and D were all more stable than paulomycin A and paulomycin B. In conclusion, without scarifying the antibacterial activity, this study increased the stability of paulomycin by the addition of paulic acid with SNAC, which laid a foundation for further research and application of paulomycins.
Key words： paulomycin; structure identification; stability; antibacterial activity
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