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嵌段共聚肽与甘露糖结合受体的定向相互作用:靶向先天免疫系统细胞的肽胶束

Directed interactions of block copolypept(o)ides with mannose-binding receptors: PeptoMicelles targeted to cells of the innate immune system.

作者信息

Heller Philipp, Mohr Nicole, Birke Alexander, Weber Benjamin, Reske-Kunz Angelika, Bros Matthias, Barz Matthias

机构信息

Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55099, Mainz, Germany.

出版信息

Macromol Biosci. 2015 Jan;15(1):63-73. doi: 10.1002/mabi.201400417. Epub 2015 Jan 5.

DOI:10.1002/mabi.201400417
PMID:25560686
Abstract

Core-shell structures based on polypept(o)ides combine stealth-like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn)) have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside as initiator in the sequential ring-opening polymerization of α-amino acid N-carboxyanhydrides. These amphiphilic block copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.

摘要

基于多肽的核壳结构将冠层材料聚肌氨酸的类隐形特性与多肽核心的可调节功能相结合。使用11-氨基-3,6,9-三氧杂十一烷基-2,3,4,6-四-O-乙酰基-O-α-D-甘露吡喃糖苷作为引发剂,通过α-氨基酸N-羧基环酐的顺序开环聚合反应合成了含甘露糖的嵌段共多肽(PSar-嵌段-PGlu(OBn))。这些两亲性嵌段共多肽自组装成多价肽胶束,并与树突状细胞表达的甘露糖结合受体结合。甘露糖化胶束在DC 2.4细胞和骨髓来源的树突状细胞(BMDC)中表现出增强的细胞摄取,因此似乎是一种适合免疫调节的平台。

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