通过铜催化的炔烃-叠氮化物1,3-偶极环加成实现肽-聚合物共轭

Peptide-Polymer Conjugation Via Copper-Catalyzed Alkyne-Azide 1,3-Dipolar Cycloaddition.

作者信息

Hussein Waleed M, Toth Istvan, Skwarczynski Mariusz

机构信息

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

出版信息

Methods Mol Biol. 2021;2355:1-7. doi: 10.1007/978-1-0716-1617-8_1.

DOI:10.1007/978-1-0716-1617-8_1

PMID:34386945

Abstract

Dendrimers are structurally well-defined, artificial polymers with physicochemical characteristics that often imitate biomacromolecules. Consequently, they are encouraging candidates for the delivery of peptide-based vaccines. We developed a synthetic protocol for conjugating a peptide antigen derived from human papillomavirus (HPV) E7 protein to a poly(t-butyl acrylate) dendrimer to construct a vaccine candidate. The synthetic pathway utilized copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) click reaction, and resulted in a 76% substitution ratio of the 8-arm dendrimer. The obtained peptide-polymer construct was self-assembled, dialyzed, and characterized by microanalysis and dynamic light scattering.

摘要

树枝状大分子是结构明确的人工聚合物，具有常模仿生物大分子的物理化学特性。因此，它们是基于肽的疫苗递送的有前景的候选物。我们开发了一种合成方案，用于将源自人乳头瘤病毒（HPV）E7蛋白的肽抗原与聚（丙烯酸叔丁酯）树枝状大分子偶联，以构建候选疫苗。合成途径利用了铜催化的炔烃-叠氮化物1,3-偶极环加成（CuAAC）点击反应，8臂树枝状大分子的取代率达到76%。所得到的肽-聚合物构建体进行了自组装、透析，并通过微量分析和动态光散射进行了表征。