Chemoenzymatic Synthesis of Asymmetrical Multi-Antennary N-Glycans to Dissect Glycan-Mediated Interactions between Human Sperm and Oocytes.
Chemoenzymatic Synthesis of Asymmetrical Multi-Antennary N-Glycans to Dissect Glycan-Mediated Interactions between Human Sperm and Oocytes.
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DOI：
10.1002/chem.201800451
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发表时间：
2018-06-04
期刊：
影响因子：
--
通讯作者：
Boons GJ
中科院分区：
文献类型：
--
作者：
Chinoy ZS;Friscourt F;Capicciotti CJ;Chiu P;Boons GJ
人卵母细胞透明带（ZP）糖蛋白的复合N-聚糖与精子结合有关。这些不寻常的双-、三-和四-触角N-聚糖的末端由四糖唾液酸-Lewisx（SLex）组成，其先前被鉴定为精子结合的最小表位。我们在此描述了高度复杂的三触角N-聚糖的化学酶法合成，这些N-聚糖衍生自ZP，在C-2和C-2′臂携带SLex部分，在C-6触角携带唾液酸-Lewisx-Lewisx（SLex-Lex）残基，以及两种密切相关的类似物。检测了化合物抑制人精子与ZP相互作用的能力。发现SLex-Lex部分对于抑制活性是关键的，而其他SLex部分发挥最小的作用。对SLex-Lex和SLex的进一步研究表明，延伸结构是更有效的抑制剂。此外，制备了三价SLex-Lex和SLex，其与其单价对应物相比显示出更大的抑制活性。我们的研究表明，虽然SLex可以抑制精子的结合，但在复杂的N-聚糖的背景下呈现该表位会导致抑制潜力的丧失，并且在这种情况下，只有SLex-Lex可以进行有效的相互作用。这不是SLex在多触角聚糖上的多价展示，而是多个SLex-Lex在ZP的各种糖基化位点上的呈递，这解释了高亲合力结合。一种化学酶的方法使得有可能制备来自人类卵母细胞的高度复杂的三触角聚糖。生物学研究表明，虽然唾液酸化Lewisx（SLex）可以抑制精子与卵母细胞的结合，但在复合N-聚糖的背景下呈递该表位会导致抑制潜力的丧失，并且在这种背景下，只有SLex-Lex表位可以产生有效的相互作用。
Complex N-glycans of glycoproteins of the zona pellucida (ZP) of human oocytes have been implicated in the binding of spermatozoa. The termini of these unusual bi-, tri-, and tetra-antennary N-glycans consist of the tetrasaccharide sialyl-Lewisx (SLex), which was previously identified as the minimal epitope for sperm binding. We describe here the chemoenzymatic synthesis of highly complex tri-antennary N-glycans derived from ZP carrying SLex moieties at the C-2 and C-2′ arm and a sialyl-Lewisx-Lewisx (SLex–Lex) residue at the C-6 antenna and two closely related analogues. The compounds were examined for their ability to inhibit the interaction of human sperm to ZP. It was found that the SLex–Lex moiety is critical for inhibitory activity, whereas the other SLex moieties exerted minimal effect. Further studies with SLex–Lex and SLex showed that the extended structure is the more potent inhibitor. In addition, trivalent SLex–Lex and SLex were prepared which showed greater inhibitory activity compared to their monovalent counterparts. Our studies show that although SLex can inhibit the binding of spermatozoa, presenting this epitope in the context of a complex N-glycan results in a loss of inhibitory potential, and in this context only SLex–Lex can make productive interactions. It is not the multivalent display of SLex on a multi-antennary glycan but the presentation of multiple SLex–Lex on the various glycosylation sites of ZP that accounts for high avidity binding. A chemoenzymatic approach made it possible to prepare highly complex tri-antennary glycans derived from human oocytes. Biological studies have shown that although sialyl Lewisx (SLex) can inhibit the binding of spermatozoa to oocytes, presenting this epitope in the context of a complex N-glycan results in a loss of inhibitory potential, and in this context only SLex–Lex epitopes can make productive interactions.
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影响因子：
4.3
作者：
MAGNANI J L
通讯作者：
MAGNANI J L
影响因子：
4.3
作者：
Serna, Sonia;Etxebarria, Juan;Reichardt, Niels-Christian
通讯作者：
Reichardt, Niels-Christian
DOI：
10.1002/mrd.1120050406
发表时间：
1982-01-01
期刊：
GAMETE RESEARCH
影响因子：
--
作者：
HUANG, TTF;OHZU, E;YANAGIMACHI, R
通讯作者：
YANAGIMACHI, R
影响因子：
6.1
作者：
LUCAS, H;BERCEGEAY, S;BARRIERE, P
通讯作者：
BARRIERE, P
影响因子：
16.6
作者：
Rillahan CD;Paulson JC
通讯作者：
Paulson JC