Development of carbohydrate-based scaffolds for restricted presentation of recognition groups. Extension to divalent ligands and implications for the structure of dimerized receptors.
Development of carbohydrate-based scaffolds for restricted presentation of recognition groups. Extension to divalent ligands and implications for the structure of dimerized receptors.
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开发基于碳水化合物的支架，用于限制识别基团的呈现。
DOI：
10.1021/jo034336d
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
W. Glass
中科院分区：
文献类型：
--
作者：
P. Murphy;H. Bradley;M. Tosin;N. Pitt;G. Fitzpatrick;W. Glass
用核磁共振研究了糖酰胺的溶液结构。一个强烈的偏好是显示由叔芳族糖基酰胺的E-反结构与仲芳族糖基酰胺，其中Z-反结构占主导地位。这些类别的分子所显示的结构多样性似乎是重要的，因为芳环或连接到芳环的基团的方向性质将通过选择在异头中心具有仲酰胺或叔酰胺来确定，并且在设计具有碳水化合物支架的生物活性分子时可以考虑。还进行了结构分析，为相关的二价仲和叔糖基酰胺和这些化合物显示类似的一价化合物的偏好。受约束的二价化合物具有促进簇的形成的潜力，所述簇将具有受限的结构，并且因此具有用于多价配体的作用机制的新研究的潜力。这些化合物的可能应用是作为设计和合成配体的支架，这些配体将促进蛋白质-蛋白质或其他受体-受体相互作用。被设计为与识别碳水化合物的蛋白质结合的限制性二价（或更高阶）配体的亲和力可能显著高于不具有这些性质的单价对应物或多价配体，所述碳水化合物将促进成簇并伴随促进蛋白质-蛋白质相互作用。这可能是有用的，作为一种新的方法，在开发基于碳水化合物的治疗。
The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein-protein or other receptor-receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein-protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.