苏州大学宣孙婷团队报道了侧链介导质子转移自促进控制叔胺悬垂多肽的开环聚合合成。相关研究成果发表在2024年10月16日出版的《德国应用化学》。

质子转移在几乎所有生物化学过程中都是必不可少的，酶通过位点特异性氢键优化反应物的接近度和方向来促进这种转移。质子转移在广泛用于制备各种拟肽材料的，N-羧酸酐（NCAs）开环聚合的速率决定步骤中也至关重要。

该研究利用侧链辅助策略，通过使用含有叔胺悬浮剂的NCAs来加速链的反应速度。该部分能够在进入的NCAs和聚合物氨基生长端之间形成氢键。NCAs的叔胺侧链通过约束较少的过渡态形成质子穿梭，以促进质子转移过程。

叔胺侧链能够在单体合成过程中通过原位质子化沉淀NCA单体。这极大地促进了这些未报告单体的合成，能够直接控制叔胺侧链多肽的合成。这种侧链促进的聚合很少有报道。此外，叔胺侧链作为广泛使用的官能团，赋予聚合物独特的性能，包括pH和热响应性、可调pKas和siRNA转染能力。自促进合成、易于制备单体和具有吸引力的性质，使叔胺侧链多肽成为各种应用的有前景的材料。

附：英文原文

Title: Self-promoted Controlled Ring-opening Polymerization via Side Chain-mediated Proton Transfer for the Synthesis of Tertiary Amine-pendant Polypeptoids

Author: Mingzhen Liao, Yao Yao, Kunyu Gan, Xianghua Su, Ning Zhao, Ronald N. Zuckermann, Sunting Xuan, Zhengbiao Zhang

Issue&Volume: 2024-10-16

Abstract: Proton transfer is essential in virtually all biochemical processes, with enzymes facilitating this transfer by optimizing the proximity and orientation of reactants through site-specific hydrogen bonds. Proton transfer is also crucial in the rate-determining step for the ring-opening polymerization of N-carboxyanhydrides (NCAs), widely used to prepare various peptidomimetic materials. This study utilizes side chain-assisted strategy to accelerate the rate of chain propagation by using NCAs with tertiary amine pendants. This moiety enables hydrogen bond formation between the incoming NCA and the polymer amino growing end. The tertiary amine side chain of the NCA forms a proton shuttle, via a less constrained transition state, to facilitate the proton transfer process. Moreover, the tertiary amine side chains enable the precipitation of NCA monomers through in situ protonation during the monomer synthesis. This greatly facilitates the synthesis of these unreported monomers, allowing the direct controlled synthesis of tertiary amine-pendant polypeptoids. This side chain-promoted polymerization has rarely been reported. Additionally, the tertiary amine side chains, as widely used functional groups, endow the polymers with unique properties including pH- and thermo-responsiveness, tunable pKas, and siRNA transfection capability. The self-promoted synthesis, facile monomer preparation, and attractive properties make tertiary amine-pendant polypeptoids promising materials for various applications.

DOI: 10.1002/anie.202417990

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202417990