Modular synthesis of N-glycans and arrays for the hetero-ligand binding analysis of HIV antibodies.
Modular synthesis of N-glycans and arrays for the hetero-ligand binding analysis of HIV antibodies.
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DOI：
10.1038/nchem.2463
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发表时间：
2016-04
期刊：
影响因子：
21.8
通讯作者：
Wong CH
中科院分区：
文献类型：
--
作者：
Shivatare SS;Chang SH;Tsai TI;Tseng SY;Shivatare VS;Lin YS;Cheng YY;Ren CT;Lee CC;Pawar S;Tsai CS;Shih HW;Zeng YF;Liang CH;Kwong PD;Burton DR;Wu CY;Wong CH
据报道，来自HIV供体的一类新的广泛中和抗体（bNAb）靶向gp 120上的聚糖，从而重新燃起了开发基于碳水化合物的HIV疫苗的希望。然而，先前研究中使用的gp 120版本不是来自人T细胞，因此糖基化模式可能与天然系统中发现的模式有些不同。此外，一些抗体同时识别两种不同的聚糖，这不能用载玻片上常用的聚糖微阵列检测。在这里，我们在氧化铝涂层的载玻片上开发了一种聚糖微阵列，其中含有一组不同的聚糖，包括通过模块化化学酶法制备的均聚和混合N-聚糖（高甘露糖、杂合和复杂类型）检测杂聚糖结合行为的存在。这种新方法可以快速筛选和鉴定中和抗体识别的最佳聚糖，并可以加速开发针对细胞表面聚糖的HIV-1疫苗。
A new class of broadly neutralizing antibodies (bNAbs) from HIV donors has been reported to target the glycans on gp120, thus renewing hope of developing carbohydrate-based HIV vaccines. However, the version of gp120 used in previous studies was not from human T cells and so the glycosylation pattern could be somewhat different to that found in the native system. Moreover, some antibodies recognized two different glycans simultaneously and this cannot be detected with the commonly used glycan microarrays on glass slides. Here, we have developed a glycan microarray on an aluminium oxide-coated glass slide containing a diverse set of glycans, including homo- and mixed N-glycans (high-mannose, hybrid and complex types) that were prepared by modular chemo-enzymatic methods to detect the presence of hetero-glycan binding behaviours. This new approach allows rapid screening and identification of optimal glycans recognized by neutralizing antibodies, and could speed up the development of HIV-1 vaccines targeting cell surface glycans.