Inhibition of a family 18 chitinase by chitooligosaccharides
Inhibition of a family 18 chitinase by chitooligosaccharides
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DOI：
10.1016/j.carbpol.2008.01.020
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发表时间：
2008-10-01
影响因子：
11.2
通讯作者：
Sorlie, Morten
中科院分区：
文献类型：
--
作者：
Cederkvist, F. Henning;Parmer, Marthe P.;Sorlie, Morten
家族18几丁质酶的抑制正在成为害虫和真菌控制以及哮喘和炎症治疗的目标。在这方面，期望获得容易产生并且具有高特异性和效率的无毒抑制剂。部分N-乙酰化的壳寡糖（CHOS）具有满足这些要求的潜力。在这项工作中，乙酰化度为0.65的高分子量壳聚糖被几丁质酶C（来自粘质沙雷氏菌的家族18内切几丁质酶）酶促降解至0.2的断裂度（裂解的糖苷键的分数）。纯化所得CHOS的聚合度（DP）。DP 5、6和8的CHOS分别与S. marcescens，几丁质酶B用作一组具有深活性位点凹槽的家族18几丁质酶的模型酶，所述家族18几丁质酶包括人酶。分离7小时后获得的产物，并使用质谱法测定其结构。所得CHOS溶液对ChiB的IC 50值在较低微摩尔范围内（15-18 μ M）。（c）2008 Elsevier Ltd.保留所有权利。
Inhibition of family 18 chitinases is emerging as a target for pest and fungal control as well as asthma and inflammatory therapy. To this regard, it is desirable to have access to non-toxic inhibitors that are easy to produce, and have high specificity and efficiency. Chitooligosaccharides (CHOS) that are partially N-acetylated have the potential to fulfill these requirements. In this work, a high molecular weight chitosan with a degree of acetylation of 0.65 was enzymatically degraded by chitinase C, a family 18 endochitinase from Serratia marcescens, to a degree of scission (the fraction of cleaved glycosidic linkages) of 0.2. The resulting CHOS were purified with respect to degree of polymerization (DP). CHOS of DP 5, 6, and 8, respectively, were allowed to interact with another type of family 18 chitinase from S. marcescens, chitinase B used as a model enzyme for a group of family 18 chitinases with deep active site grooves that includes human enzymes. Products obtained after 7 h were isolated and their structures were determined using mass spectrometry. The IC50-values of the resulting CHOS solutions for ChiB were in the lower micromolar range (15-18 mu M), (c) 2008 Elsevier Ltd. All rights reserved.