Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2-3Galbeta1-3GalNAc sequences.
Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2-3Galbeta1-3GalNAc sequences.
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通过合理合成的新型核心 2 样分支结构（包含 GalNAc-Lewisx 和 Neu5Acalpha2-3Galbeta1-3GalNAc 序列）抑制 L-和 P-选择素。
DOI：
10.1093/glycob/8.7.707
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发表时间：
1998
期刊：
影响因子：
4.3
通讯作者：
Matta,KL
中科院分区：
文献类型：
--
作者：
Jain,RK;Piskorz,CF;Huang,BG;Locke,RD;Han,HL;Koenig,A;Varki,A;Matta,KL
选择素在重要的正常和病理情况下与含有唾液酸Lewisx(Neu5Acα2–3Galβ1–4(Fuc-α1–3)GlcNAc)的某些唾液酸化、岩藻糖基化糖缀合物配体相互作用。人们在合成唾液酸化和硫酸化的Lewisx类似物作为选择素的竞争性配体方面付出了很大的努力。由于天然选择素配体 GlyCAM-1 和 PSGL-1 携带唾液酸 Lewisx 作为支链 Core 2 O 连接结构的一部分，我们最近合成了 Galβ1–4(Fuc-α1–3)GlcNAcβ1–6(SE-3Galβ1–3)GalNAc1αOMe 并发现它是 L 和 P-选择素的适度优质配体。其他研究表明，硫酸酯可以取代某些选择素配体中的唾液酸（Yeunet al., Biochemistry, 31, 9126–9131, 1992；）。基于这些观察，我们假设 Neu5Acα2–3Galβ1–3Gal-NAc 可能具有与 L-和 P-选择素相互作用的能力。为了检验这一假设，我们合成了 Galβ1–4(Fucα1–3)GlcNAcβ1–6(Neu5Acα2–3Galβ1–3)-Gal-NAca1-OB，发现其对于 P 和 L 选择素的效果分别比唾液酸 Lex 好 2 至 3 倍。我们还报道了一种不寻常结构 GalNAcβ1–4(Fucα1–3)GlcNAcβ1-OMe（GalNAc-Lewisx-O-甲基糖苷）的合成，该结构也被证明是比唾液酸 Lewisx-OMe 更好的 L-和 P-选择素抑制剂。结合我们对Core 2支链结构的了解，我们合成了一种比唾液酸Lewisx-OMe抑制L-和P-选择素效果好5至6倍的分子。与非支链结构相比，用硫酸酯基团取代此类分子中的唾液酸残基会导致抑制能力的显着损失。因此，主臂 (β1-3) 臂上的唾液酸残基与 O 连接核心 2 结构上分支 (β1-6) 臂上的修饰 Lexunit 的组合产生了一种单价合成低聚糖抑制剂，其对于 L-和 P-选择素均优于 SLex。
The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acα2–3Galβ1–4(Fuc-α1–3)GlcNAc). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galβ1–4(Fuc-α1–3)GlcNAcβ1–6(SE-3Galβ1–3)GalNAc1αOMe and found it to be a moderately superior ligand for L and P-selectin . Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeunet al., Biochemistry, 31, 9126–9131, 1992; ). Based upon these observations, we hypothesized that Neu5Acα2–3Galβ1–3Gal-NAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galβ1–4(Fucα1–3)GlcNAcβ1–6(Neu5Acα2–3Galβ1–3)-Gal- NAca1-OB, which was found to be 2- to 3-fold better than sialyl Lex for P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcβ1–4(Fucα1–3)GlcNAcβ1-OMe (GalNAc-Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe,By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (β1–3) arm, and a modified Lexunit on the branched (β1–6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior toSLexfor both L- and P-selectin.
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影响因子：
64.8
作者：
Y. Lmai;L. Lasky;S. Rosen
通讯作者：
Y. Lmai;L. Lasky;S. Rosen
6-硫酸化唾液酸-Lewisx 的酶促合成，它是 L-选择素与外周地址素结合的抑制剂。
影响因子：
4.3
作者：
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DOI：
--
发表时间：
1996
期刊：
影响因子：
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影响因子：
4.3
作者：
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DOI：
10.1016/s1044-5781(06)80022-8
发表时间：
1995
期刊：
Seminars in Developmental Biology
影响因子：
--
作者：
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通讯作者：
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