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采用新型碳水化合物支架构建自佐剂脂肽疫苗的汇聚合成方法。

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold.

机构信息

The University of Queensland, School of Chemistry and Molecular Biosciences, Cooper Road, St. Lucia QLD 4072, Australia.

The University of Queensland, School of Chemistry and Molecular Biosciences, Cooper Road, St. Lucia QLD 4072, Australia ; The University of Queensland, School of Pharmacy, Pharmacy Australia Centre of Excellence, Cornwall Street, Woolloongabba, QLD 4072, Australia.

出版信息

Beilstein J Org Chem. 2014 Jul 30;10:1741-8. doi: 10.3762/bjoc.10.181. eCollection 2014.

Abstract

A novel convergent synthetic strategy for the construction of multicomponent self-adjuvanting lipopeptide vaccines was developed. A tetraalkyne-functionalized glucose derivative and lipidated Fmoc-lysine were prepared by novel efficient and convenient syntheses. The carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines) on solid support. Four copies of a group A streptococcal B cell epitope (J8) were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated by the preparation of a second vaccine candidate which incorporated an additional promiscuous T-helper epitope.

摘要

开发了一种新颖的用于构建多组分自佐剂脂肽疫苗的收敛综合策略。通过新颖的高效便捷合成,制备了四炔基功能化葡萄糖衍生物和脂质化 Fmoc-赖氨酸。碳水化合物砌块在固体载体上与自佐剂脂质部分(三个脂质化 Fmoc-赖氨酸)偶联。然后,使用铜催化的环加成反应将四组 A 群链球菌 B 细胞表位(J8)连接到糖脂肽上。该方法通过制备第二个疫苗候选物得到了详细阐述,其中包含了另外一个混杂的 T 辅助表位。

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