侧链功能化的α-螺旋多肽的一般路线。

General route toward side-chain-functionalized alpha-helical polypeptides.

机构信息

Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, USA.

出版信息

Biomacromolecules. 2010 Jun 14;11(6):1585-92. doi: 10.1021/bm1002174.

DOI:10.1021/bm1002174

PMID:20465286

Abstract

A series of poly(gamma-chloropropyl-L-glutamate) (PCPLG) with controlled polymer molecular weight (MW = 5-28 kg x mol(-1)) and molecular weight distribution (PDI = 1.16-1.26) have been prepared from hexamethyldisilazane (HMDS)-mediated ring-opening polymerization (ROP) of gamma-chloropropyl-L-glutamic acid based N-carboxylanhydride (CP-NCA). CD, FTIR, and WAXS analysis reveal that the polymers adopt alpha-helical conformations both in solution and the solid state. Their helical surfaces can be readily decorated with functional moieties to confer desired properties, as demonstrated by the quantitative derivatization of the PCPLG side chains with azido functional groups that are amendable to "click" chemistry. Subsequent side-chain conjugation with mannose moieties via copper-mediated [2 + 3] alkyne-azide 1,3-dipolar cycloaddition affords water-soluble mannose-polypeptide conjugates with quantitative grafting efficiency occurring under mild conditions. CD analysis reveals that the mannose-polypeptide conjugates also retain alpha-helical conformations in aqueous solution.

摘要

已经通过六甲基二硅氮烷（HMDS）介导的γ-氯丙酰基-L-谷氨酸 N-羧基酐（CP-NCA）的开环聚合（ROP）制备了一系列具有受控聚合物分子量（MW = 5-28 kg x mol(-1)) 和分子量分布（PDI = 1.16-1.26）的聚（γ-氯丙基-L-谷氨酸）（PCPLG）。CD、FTIR 和 WAXS 分析表明，聚合物在溶液和固态中均采用α-螺旋构象。它们的螺旋表面可以很容易地用功能基团修饰，以赋予所需的性质，这可以通过定量衍生聚（PCPLG）侧链上的叠氮官能团来证明，这些叠氮官能团适合“点击”化学。随后通过铜介导的[2 + 3]炔基-叠氮 1,3-偶极环加成反应将甘露糖部分与侧链共轭，在温和条件下可定量接枝，接枝效率很高。CD 分析表明，甘露糖-多肽缀合物在水溶液中也保留α-螺旋构象。