Multivalent glycocluster design through directed evolution.
Multivalent glycocluster design through directed evolution.
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DOI：
10.1002/anie.201105555
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发表时间：
2011-11-18
影响因子：
16.6
通讯作者：
Krauss, Isaac J.
中科院分区：
文献类型：
--
作者：
MacPherson, Iain S.;Temme, J. Sebastian;Habeshian, Sevan;Felczak, Krzysztof;Pankiewicz, Krzysztof;Hedstrom, Lizbeth;Krauss, Isaac J.
大量的生物过程是由多价配体-受体相互作用介导的，包括细胞粘附、病原体入侵宿主、宿主中和病原体和许多细胞调节信号通路多价性对于碳水化合物与受体的相互作用尤为重要：尽管单个聚糖[2]可能以低亲和力与单一结合位点结合，但聚糖的聚类却能与聚类结合位点产生高亲和力的相互作用。这种“碳水化合物簇效应”[1b]已经通过合成的多价碳水化合物配体得到了实验证明，这些配体与蛋白质靶标结合良好。这些配体包括不同支架上的寡价和多价聚糖簇，包括小分子、树状大分子、聚合物甚至病毒衣壳。迄今为止，大多数糖簇配体都是为了合成方便而设计的，而不是为了控制三级结构。然而，天然糖簇的生物活性可能会受到三级结构和其他合成糖簇设计中通常不考虑的因素的影响，例如：1)聚糖的间距和方向-聚糖通常通过长柔性连接剂附着在合成支架上，而支架本身通常是柔性的。2)天然糖簇中多糖的内部柔韧性
A vast number of biological processes are mediated by multivalent ligand-receptor interactions, including cell adhesion, host invasion by pathogens, pathogen neutralization by host and numerous cell regulatory signaling pathways.[1] Multivalency is especially important for carbohydrate-receptor interactions: whereas individual glycans [2] may bind with low affinity to a single binding site, the clustering of glycans creates a high-avidity interaction with clustered binding sites. This “carbohydrate cluster effect”[1b] has been demonstrated experimentally with synthetic multivalent carbohydrate ligands which bind well to protein targets. These ligands have included oligo-and polyvalent clusters of glycans on diverse scaffolds, including small molecules, dendrimers, polymers and even viral capsids.To date, most glycocluster ligands have been designed for synthetic convenience rather than control of tertiary structure. However, the biological activity of the natural glycocluster may be influenced by tertiary structure and other elements which are not usually addressed in synthetic glycocluster designs, such as: 1) Glycan spacing and orientation–glycans are normally attached to synthetic scaffolds through long flexible linkers, and the scaffolds themselves are often flexible.[3] 2) Glycan internal flexibility–in a natural glycocluster,
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影响因子：
1.8
作者：
Iserloh, U;Dudkin, V;Danishefsky, SJ
通讯作者：
Danishefsky, SJ
影响因子：
--
作者：
Astronomo RD;Kaltgrad E;Udit AK;Wang SK;Doores KJ;Huang CY;Pantophlet R;Paulson JC;Wong CH;Finn MG;Burton DR
通讯作者：
Burton DR
影响因子：
15
作者：
Li, Minyong;Lin, Na;Huang, Zhen;Du, Lupei;Altier, Craig;Fang, Hao;Wang, Binghe
通讯作者：
Wang, Binghe
影响因子：
3.6
作者：
Crich, D;Sun, SX
通讯作者：
Sun, SX
影响因子：
16.6
作者：
Geng, XD;Dudkin, VY;Danishefsky, SJ
通讯作者：
Danishefsky, SJ