Cheng Zihe, Song Qiao, Hall Stephen C L, Perrier Sébastien
Department of Chemistry, University of Warwick Coventry CV4 7AL UK
Shenzhen Grubbs Institute, Southern University of Science and Technology Shenzhen 518055 China.
Chem Sci. 2024 Dec 17;16(4):1894-1906. doi: 10.1039/d4sc06288d. eCollection 2025 Jan 22.
Self-assembling cyclic peptide nanotubes are fascinating supramolecular systems with promising potential for various applications, such as drug delivery, transmembrane ionic channels, and artificial light-harvesting systems. In this study, we present novel pH-responsive nanotubes based on asymmetric cyclic peptide-polymer conjugates. The pH response is introduced by a tertiary amine-based polymer, poly(dimethylamino ethyl methacrylate) (pDMAEMA) or poly(diethylamino ethyl methacrylate) (pDEAEMA) which is protonated at low pH. The self-assembling behaviour of their corresponding conjugates is investigated using different scattering and spectroscopy techniques. Compared to conjugates with hydrophilic polymeric corona, the introduction of hydrophobic polymer chains on the periphery of the cyclic peptides can prevent water molecules from penetrating through to the peptide rings, allowing the construction of hydrogen bonding interactions between cyclic peptides to form longer nanotubes. The switching between assembly and non-assembly is triggered by the change in the surrounding environmental pH, which process is controlled by the coordination between hydrophobic interactions and electrostatic repulsions. Due to the different hydrophobicity of these two polymers, the self-assembly of their corresponding conjugates varies extensively. We first demonstrate this evolution in detail and describe the relationship between the self-assembly and the inherent properties of grafted polymers, such as polymer compositions, the protonation degree of the responsive polymers and the polymer molecular weight in solutions.
自组装环状肽纳米管是迷人的超分子体系,在药物递送、跨膜离子通道和人工光捕获系统等各种应用中具有广阔的潜在应用前景。在本研究中,我们展示了基于不对称环状肽 - 聚合物共轭物的新型pH响应性纳米管。pH响应是由基于叔胺的聚合物聚(甲基丙烯酸二甲氨基乙酯)(pDMAEMA)或聚(甲基丙烯酸二乙氨基乙酯)(pDEAEMA)引入的,它们在低pH下会质子化。使用不同的散射和光谱技术研究了它们相应共轭物的自组装行为。与具有亲水性聚合物冠层的共轭物相比,在环状肽外围引入疏水性聚合物链可以防止水分子渗透到肽环中,从而允许在环状肽之间构建氢键相互作用以形成更长的纳米管。组装和非组装之间的切换由周围环境pH的变化触发,这一过程由疏水相互作用和静电排斥之间的协同作用控制。由于这两种聚合物的疏水性不同,它们相应共轭物的自组装有很大差异。我们首先详细展示了这种演变,并描述了自组装与接枝聚合物固有性质之间的关系,如聚合物组成、响应性聚合物的质子化程度以及溶液中的聚合物分子量。