Murphy Paul V, Bradley Helena, Tosin Manuela, Pitt Nigel, Fitzpatrick Geraldine M, Glass W Kenneth
Chemistry Department, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
J Org Chem. 2003 Jul 11;68(14):5692-704. doi: 10.1021/jo034336d.
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.
已通过核磁共振研究了糖基酰胺的溶液结构。与主要为Z-反式结构的仲芳基糖基酰胺相比，叔芳基糖基酰胺对E-反式结构表现出强烈偏好。这些类型分子所呈现的结构多样性似乎很重要，因为芳环或连接在芳环上的基团的方向性特性，将通过在异头中心选择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加以考虑。还对相关的二价仲糖基酰胺和叔糖基酰胺进行了结构分析，这些化合物表现出与单价化合物相似的偏好。受约束的二价化合物具有促进形成具有受限结构的簇的潜力，因此具有对多价配体作用机制进行新颖研究的潜力。此类化合物的可能应用是作为设计和合成配体的支架，以促进蛋白质-蛋白质或其他受体-受体相互作用。设计用于结合识别碳水化合物的蛋白质以促进聚集并同时促进蛋白质-蛋白质相互作用的受限二价（或更高价）配体的亲和力，可能显著高于单价对应物或没有这些特性的多价配体。这可能作为基于碳水化合物的治疗药物开发的一种新方法而有用。
