Holm Regina, Klinker Kristina, Weber Benjamin, Barz Matthias
Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128, Mainz, Germany.
Macromol Rapid Commun. 2015 Dec;36(23):2083-91. doi: 10.1002/marc.201500402. Epub 2015 Sep 7.
In this work, the synthesis of polypeptoid-block-polypeptide copolymers (block copolypept(o)ides) based on bifunctional initiators is described, which introduces a distinct chemical entity at the connection between both blocks. With a view towards redox-sensitive block copolypept(o)ides, a cystamine-based initiator was used to synthesize polysarcosine macroinitiators with degrees of polymerization (Xn) between 100 and 200 displaying monomodal molecular weight distributions and dispersities (Đ) around 1.1 as determined by size exclusion chromatography. Block copolypept(o)ides with a poly(γ-t-butyloxycarbonyl-L-glutamate) (PGlu(O(t) Bu)) block (Xn = 25 or 50) were synthesized by controlled N-carboxyanhydride polymerization. Resulting block copolymers possess monomodal molecular weight distributions, dispersities around 1.2 and were applied to degradation studies. While block copolypept(o)ides are stable at 10 × 10(-6) M, they degrade over time at GSH concentrations of 10 × 10(-3) and 100 × 10(-3) M. Furthermore, these disulfide-containing block copolymers form PeptoMicelles, which degrade at intracellular GSH concentrations while remaining stable at extracellular GSH levels.
在这项工作中，描述了基于双功能引发剂合成聚肽类-嵌段-多肽共聚物（嵌段共聚肽）的方法，该方法在两个嵌段之间的连接处引入了一个独特的化学实体。为了合成对氧化还原敏感的嵌段共聚肽，使用了基于胱胺的引发剂来合成聚合度（Xn）在100至200之间的聚肌氨酸大分子引发剂，通过尺寸排阻色谱法测定，其显示出单峰分子量分布且分散度（Đ）约为1.1。通过可控的N-羧基环内酸酐聚合反应合成了具有聚（γ-叔丁氧羰基-L-谷氨酸）（PGlu（O（t）Bu））嵌段（Xn = 25或50）的嵌段共聚肽。所得的嵌段共聚物具有单峰分子量分布，分散度约为1.2，并应用于降解研究。虽然嵌段共聚肽在10×10（-6）M时稳定，但在10×10（-3）M和100×10（-3）M的谷胱甘肽浓度下会随时间降解。此外，这些含二硫键的嵌段共聚物形成肽胶束，其在细胞内谷胱甘肽浓度下会降解，而在细胞外谷胱甘肽水平下保持稳定。
