Tailored design and synthesis of heparan sulfate oligosaccharide analogues using sequential one-pot multienzyme systems.
Tailored design and synthesis of heparan sulfate oligosaccharide analogues using sequential one-pot multienzyme systems.
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DOI：
10.1002/anie.201305667
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发表时间：
2013-11-04
影响因子：
16.6
通讯作者：
Chen, Xi
中科院分区：
文献类型：
--
作者：
Chen, Yi;Li, Yanhong;Yu, Hai;Sugiarto, Go;Thon, Vireak;Hwang, Joel;Ding, Li;Hie, Liana;Chen, Xi
硫酸乙酰肝素（HS）和肝素是线性硫酸化杂多糖，由交替的α1-4-连接D-葡糖胺（GlcN）和1-4-连接糖醛酸（L-艾杜糖醛酸IdoA的α-连接和D-葡糖醛酸GlcA的β-连接）组成。可能的修饰是糖醛酸残基上的2-O-硫酸化和葡糖胺残基上的一种或多种修饰，包括N-硫酸化、N-乙酰化、6-O-硫酸化和3-O-硫酸化。肝素和低分子量肝素（LMWH）是最常用的抗凝剂或抗血栓药物。与HS相比，肝素具有更高的硫酸化水平和更高的IdoA含量。[1]肝素主要由肥大细胞产生，硫酸乙酰肝素由动物中不同类型的细胞产生。[2]由于肝素的治疗应用，以及HS和肝素在调节癌症生长、血液凝固、炎症、辅助病毒和细菌感染、信号转导、脂质代谢和细胞分化中的重要作用，它们是有吸引力的合成靶标。[3]合成肝素可以消除从天然来源纯化的固有异质肝素引起的副作用。然而，由于它们的结构复杂性，它们的合成具有很大的合成挑战。虽然在过去的十年里，HS/肝素复合物的合成、分析和理解取得了很大进展，但HS/肝素复合物的形成和调控机制以及HS/肝素复合物的结构-功能关系仍然没有完全了解。[2]目前仍然缺乏一种量身定制的合成工艺。
Heparan sulfate (HS) and heparin are linear sulfated heteropolysaccharides consisting of alternating α1–4-linked D-glucosamine (GlcN) and 1–4-linked uronic acid (α-linkage for L-iduronic acid, IdoA, and β-linkage for D-glucuronic acid, GlcA). Possible modifications are 2-O-sulfation on the uronic acid residues and one or more modifications on the glucosamine residues including N-sulfation, N-acetylation, 6-O-sulfation, and 3-O-sulfation. Heparin and low molecular weight heparin (LMWH) are the most commonly used anticoagulants or antithrombotic drugs. Compared to HS, heparin has a higher level of sulfation and a higher IdoA content.[1] Heparin is mostly produced by mast cells and heparan sulfates are produced by different cell types in animals.[2] They are attractive synthetic targets due to the therapeutic application of heparin, and the important roles of HS and heparin in regulating cancer growth, blood coagulation, inflammation, assisting viral and bacterial infections, signal transduction, lipid metabolism, and cell differentiation.[3]Synthetic heparins can eliminate the side effects caused by inherent heterogeneous heparins purified from natural sources. Their synthesis, however, possesses great synthetic challenges due to their structural complexity. Although much progress has been made over the last decade on the synthesis, analysis, and understanding of complex HS and heparin, the mechanisms for the formation and regulation of HS/heparin and the structure-function relationship of complex HS/heparin are still not fully understood.[2] A tailor-made synthetic process is still lacking.
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影响因子：
5
作者：
Li, Yanhong;Yu, Hai;Thon, Vireak;Chen, Yi;Muthana, Musleh M.;Qu, Jingyao;Hie, Liana;Chen, Xi
通讯作者：
Chen, Xi
影响因子：
2.7
作者：
Chen, Chen;Yu, Biao
通讯作者：
Yu, Biao
影响因子：
3
作者：
Ojeda, R;Terentí, O;Martín-Lomas, M
通讯作者：
Martín-Lomas, M
影响因子：
15
作者：
Arungundram, Sailaja;Al-Mafraji, Kanar;Asong, Jinkeng;Leach, Franklin E., III;Amster, I. Jonathan;Venot, Andre;Turnbull, Jeremy E.;Boons, Geert-Jan
通讯作者：
Boons, Geert-Jan
影响因子：
15
作者：
de Paz, JL;Noti, C;Seeberger, PH
通讯作者：
Seeberger, PH