Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody
Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody
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DOI：
10.1021/ja074804r
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发表时间：
2007-09-12
影响因子：
15
通讯作者：
Danishefsky, Samuel J.
中科院分区：
文献类型：
--
作者：
Krauss, Isaac J.;Joyce, Joseph G.;Danishefsky, Samuel J.
已经合成了HIV 2G 12表位的二价和三价糖肽模拟物，并评价了它们的比较2G 12结合特性。表位模拟物由通过天冬氨酸键与两个或三个拷贝的高甘露糖聚糖Man（9）GlcNAc（2）连接的环状肽支架（与gp 120肽序列无关）组成。通过Man（9）GlcNAc（2）-NH 2与分别含有两个和三个天冬氨酸残基的肽的高产率双重和三重Lansbury双酰化来实现合成。这种构建体与免疫原性载体蛋白OMPC的缀合已经通过肽的半胱氨酸巯基功能完成，并且Biacore测定已经显示对2G 12的结合亲和力随着化合价的增加而增加。
Di- and trivalent glycopeptide mimics of the HIV 2G12 epitope have been synthesized and evaluated for their comparative 2G12 binding characteristics. The epitope mimics consist of a cyclic peptide scaffold (unrelated to gp120 peptide sequences) attached via aspartate linkages to two or three copies of the high-mannose glycan, Man(9)GlcNAc(2). The synthesis has been achieved via high-yielding double and triple Lansbury aspartylations of Man(9)GlcNAc(2)-NH2 with peptides containing, respectively, two and three aspartate residues. Conjugation of such constructs with an immunogenic carrier protein, OMPC, has been accomplished through the peptide's cysteine sulfhydryl function, and Biacore assays have shown that binding affinity for 2G12 increases with increasing valency.