基于甘露糖的 DC-SIGN 拮抗剂的设计、合成与活性评价。
Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists.
机构信息
Department of Biotechnology, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
出版信息
Mol Divers. 2011 May;15(2):347-60. doi: 10.1007/s11030-010-9285-y. Epub 2010 Nov 14.
Abstract
In this article, we describe the design, synthesis and activity evaluation of glycomimetic DC-SIGN antagonists, that use a mannose residue to anchor to the protein carbohydrate recognition domain (CRD). The molecules were designed from the structure of the known pseudo-mannobioside antagonist 1, by including additional hydrophobic groups, which were expected to engage lipophilic areas of DC-SIGN CRD. The results demonstrate that the synthesized compounds potently inhibit DC-SIGN-mediated adhesion to mannan coated plates. Additionally, in silico docking studies were performed to rationalize the results and to suggest further optimization.
摘要
在本文中，我们描述了糖模拟物 DC-SIGN 拮抗剂的设计、合成和活性评估，这些拮抗剂使用甘露糖残基锚定到蛋白质碳水化合物识别域 (CRD)。这些分子是根据已知的假甘露糖苷拮抗剂 1 的结构设计的，通过引入额外的疏水性基团，预计这些基团将与 DC-SIGN CRD 的亲脂区域结合。结果表明，合成的化合物能强烈抑制 DC-SIGN 介导的甘露聚糖包被板的黏附。此外，还进行了计算机对接研究，以合理化结果并提出进一步的优化。
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