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Updated: May 3, 2026

Chemo-enzymatic Synthesis of N-glycans for Array Development and HIV Antibody Profiling

Chemo-enzymatic Synthesis of N-glycans for Array Development and HIV Antibody Profiling

Published on: February 5, 2018

高温SELMA:DNA支持的寡曼诺集群的演化,这些由HIV bnAb 2G12密切识别

J Sebastian Temme¹, Iain S MacPherson, John F DeCourcey

¹Department of Chemistry, Brandeis University , Waltham, Massachusetts, 02454-9110, United States.

Journal of the American Chemical Society

|January 23, 2014

概括

经过修改的阿帕特马选择 (SELMA) 创建了强大的碳水化合物集群,用于HIV抗体识别. 这些新的葡萄糖集群表现出100倍强的结合与更少的甘氨酸,为HIV免疫原体的发展提供了希望.

科学领域:

碳水化合物化学碳水化合物化学
免疫学免疫学免疫学
生物技术是生物技术.

背景情况:

像SELMA这样的定向进化方法优化了DNA支持的碳水化合物集群以识别莱克.
之前的SELMA应用产生了由HIV抗体2G12识别的中度亲和力的寡曼诺糖干.
艾滋病毒抗体2G12向HIV包膜蛋白 gp120.20上的保存表位.

研究的目的:

开发一个修改后的SELMA方法,以改进葡萄糖集群设计.
创建具有显著改进的结合亲和力和降低的甘氨酸密度的新型葡萄糖集群.
调查这些优化的葡萄糖集群作为免疫因子的潜力,以引起对艾滋病毒的广泛中和抗体.

主要方法:

用修改的阿普塔默 (SELMA) 技术对SELection进行修改.
合成DNA支持的葡萄糖集群,其中含有不同数量的寡甘糖.
使用表面等离子体共振或类似技术量化抗体-甘氨酸相互作用的亲和度测量 (Kd).
通过广泛中和性HIV抗体2G12.2G12对葡萄糖集团识别的评估.

主要成果:

与以前的方法相比,修改后的SELMA方法产生了100倍增加目标识别的糖分群.
这些新型的葡萄糖集群需要显著减少的葡萄糖 (3-4单位) 强度的结合.
葡萄糖集群表现出低纳米分离常数 (Kd低至1.7nM) 与HIV抗体2G12.
优化的葡萄糖集群所获得的结合亲和力与原生HIV包膜蛋白gp120.

结论:

修改后的SELMA方法可以创建高强度的葡萄糖集群,最小的葡萄糖成分.
这些优化的葡萄糖集群代表了针对HIV抗体2G12.2的重大进步.
开发的葡萄糖集群是有希望的候选人,可以用作免疫原来诱导广泛中和的HIV抗体.

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