Sbordone Federica, Veskova Juliet, Richardson Bailey, Do Phuong Thi, Micallef Aaron, Frisch Hendrik
School of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD 4000, Australia.
Centre for Materials Science, Queensland University of Technology, Brisbane, QLD 4000, Australia.
J Am Chem Soc. 2023 Mar 22;145(11):6221-6229. doi: 10.1021/jacs.2c12517. Epub 2023 Mar 10.
Biopolymers such as proteins and nucleic acids are the key building blocks of life. Synthetic polymers have nevertheless revolutionized our everyday life through their robust synthetic accessibility. Combining the unmatched functionality of biopolymers with the robustness of tailorable synthetic polymers holds the promise to create materials that can be designed ad hoc for a wide array of applications. Radical polymerization is the most widely applied polymerization technique in both fundamental science and industrial polymer production. While this polymerization technique is robust and well controlled, it generally yields unfunctional all-carbon backbones. Combinations of natural polymers such as peptides, with synthetic polymers, are thus limited to tethering peptides onto the side chains or chain ends of the latter. This synthetic limitation is a critical restraint, considering that the function of biopolymers is programmed into the sequence of their main chain (i.e., primary structure). Here, we report the radical copolymerization of peptides and synthetic comonomers yielding synthetic polymers with defined peptide sequences embedded into their main chain. Key was the development of a solid-phase peptide synthesis (SPPS) approach to generate synthetic access to peptide conjugates containing allylic sulfides. Following cyclization, the obtained peptide monomers can be readily copolymerized with ,-dimethylacrylamide (DMA)─controlled by reversible addition-fragmentation chain transfer (RAFT). Importantly, the developed synthetic strategy is compatible with all 20 standard amino acids and uses exclusively standard SPPS chemicals or chemicals accessible in one-step synthesis─prerequisite for widespread and universal application.
蛋白质和核酸等生物聚合物是生命的关键组成部分。然而，合成聚合物凭借其强大的合成可及性彻底改变了我们的日常生活。将生物聚合物无与伦比的功能与可定制合成聚合物的坚固性相结合，有望创造出能够针对广泛应用进行特殊设计的材料。自由基聚合是基础科学和工业聚合物生产中应用最广泛的聚合技术。虽然这种聚合技术强大且可控，但它通常会产生无功能的全碳主链。因此，诸如肽等天然聚合物与合成聚合物的组合仅限于将肽连接到后者的侧链或链端。考虑到生物聚合物的功能是由其主链序列（即一级结构）决定的，这种合成限制是一个关键制约因素。在此，我们报道了肽与合成共聚单体的自由基共聚反应，生成主链中嵌入特定肽序列的合成聚合物。关键在于开发一种固相肽合成（SPPS）方法，以实现对含有烯丙基硫醚的肽缀合物的合成。环化后，所得肽单体可通过可逆加成-断裂链转移（RAFT）与N,N-二甲基丙烯酰胺（DMA）轻松共聚。重要的是，所开发的合成策略与所有20种标准氨基酸兼容，并且仅使用标准的SPPS化学品或一步合成中可获得的化学品，这是广泛和普遍应用的先决条件。
