Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.
Biomacromolecules. 2020 Sep 14;21(9):3878-3886. doi: 10.1021/acs.biomac.0c00962. Epub 2020 Aug 5.
High molecular weight, synthetic block copolypeptides that self-assemble are in high demand for biomedical applications. The current standard method for synthesis of block copolypeptides is the controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydride (NCA) monomers, where block architectures can be created by sequential NCA monomer addition. Recently, researchers have focused on developing reaction conditions and initiation systems that make NCA ROP more convenient, particularly for interdisciplinary labs without designated polypeptide facilities. In an effort to further simplify and increase the convenience of polypeptide synthesis, we developed a one-shot copolymerization strategy that allows access to block copolypeptides by capitalizing on the inherently faster reactivity of NCA monomers, compared to NTA (N-carboxyanhydride) monomers. For the first time, we combine an NCA and NTA monomer in one reaction to kinetically promote block copolypeptide formation, providing a convenient alternative to sequential monomer addition. The controlled nature of this copolymerization technique is supported by a molecular weight that is modulated by the concentration of the initiator and low dispersities. We used this one-shot copolymerization to synthesize p(lysine)--p(leucine), a known peptide amphiphile (PA). Our one-shot PAs are antimicrobial and can spontaneously form ordered, micron-scale assemblies. Covalent conjugation of one-shot PAs to a graphenic backbone results in a functional graphenic material (FGM) with a self-assembled morphology, paving the way for creation of sophisticated FGM scaffolds with polypeptide-templated, hierarchical order. Overall, we demonstrate that this novel, one-shot copolymerization strategy produces functional copolypeptides with macroscopic sequence control.
高分子量、可自组装的合成嵌段共多肽在生物医学应用中需求量很大。目前合成嵌段共多肽的标准方法是通过α-氨基酸 N-羧酸酐（NCA）单体的受控开环聚合（ROP），其中可以通过顺序添加 NCA 单体来创建嵌段结构。最近，研究人员专注于开发反应条件和引发体系，使 NCA ROP 更加方便，特别是对于没有指定多肽设施的跨学科实验室。为了进一步简化和提高多肽合成的便利性，我们开发了一种一步共聚策略，通过利用 NCA 单体与 NTA（N-羧酸酐）单体相比固有更快的反应性，来获得嵌段共多肽。我们首次在一个反应中结合 NCA 和 NTA 单体，通过动力学促进嵌段共聚物的形成，为顺序单体添加提供了一种方便的替代方法。这种共聚技术的可控性得到了分子量的支持，分子量可以通过引发剂的浓度和低分散度来调节。我们使用这种一步共聚法合成了 p(赖氨酸)-p(亮氨酸)，这是一种已知的肽两亲物（PA）。我们的一次性 PA 具有抗菌性，可以自发形成有序的、微米级的组装体。将一次性 PA 共价连接到石墨骨架上，得到具有自组装形态的功能性石墨材料（FGM），为创建具有多肽模板、层次有序的复杂 FGM 支架铺平了道路。总的来说，我们证明了这种新颖的一步共聚策略可以产生具有宏观序列控制的功能性共多肽。
