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首页> 外文期刊>Chemistry: A European journal >The Impact of Heteromultivalency in Lectin Recognition and Glycosidase Inhibition: An Integrated Mechanistic Study
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The Impact of Heteromultivalency in Lectin Recognition and Glycosidase Inhibition: An Integrated Mechanistic Study

机译：异素识别和糖苷酶抑制作用的影响：综合机械研究

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The vision of multivalency as a strategy limited to achieve affinity enhancements between a protein receptor and its putative sugar ligand (glycotope) has proven too simplistic. On the one hand, binding of a glycotope in a dense glycocalix-like construct to a lectin partner has been shown to be sensitive to the presence of a third sugar entity (heterocluster effect). On the other hand, several carbohydrate processing enzymes (glycosidases and glycosyltransferases) have been found to be also responsive to multivalent presentations of binding partners (multivalent enzyme inhibition), a phenomenon first discovered for iminosugar-type inhibitory species (inhitopes) and recently demonstrated for multivalent carbohydrate constructs. By assessing a series of homo- and heteroclusters combining α-d-glucopyranosyl-related glycotopes and inhitopes, it was shown that multivalency and heteromultivalency govern both kinds of events, allowing for activation, deactivation or enhancement of specific recognition phenomena towards a spectrum of lectin and glycosidase partners in a multimodal manner. This unified scenario originates from the ability of (hetero)multivalent architectures to trigger glycosidase binding modes that are reminiscent of those harnessed by lectins, which should be considered when profiling the biological activity of multivalent architectures.
机译：以蛋白质受体与其推定的糖配体（GlycoTope）之间实现亲和力增强的策略的多价的视野已经证明了太简单。一方面，已经显示出与凝集素合作蛋白的致密糖醛橡胶状构建体中的糖蛋白的结合已被证明对第三糖实体（杂蛋白效应）的存在敏感。另一方面，已发现几种碳水化合物加工酶（糖苷酶和糖基三烷基酶）也响应于结合伴侣（多价酶抑制）的多价呈递，首先发现了用于Iminosugar型抑制物种（inhitopes）的现象，最近证明多价碳水化合物构建体。通过评估组合α-D-吡喃葡萄糖基相关的糖素和烟型的一系列同性恋和杂蛋白，结果表明，多价和异级等维生力治理两种事件，允许激活，停用或提高特定识别现象对凝集素的光谱和糖苷酶伴侣以多式联形方式。该统一场景起源于（异质）多价架构来引发糖苷酶结合模式，这些模式使凝胶素利用的那些引发，当分析多价架构的生物活性时应考虑。

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