Catrouillet Sylvain, Brendel Johannes C, Larnaudie Sophie, Barlow Tammie, Jolliffe Katrina A, Perrier Sébastien
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, United Kingdom.
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
ACS Macro Lett. 2016 Oct 18;5(10):1119-1123. doi: 10.1021/acsmacrolett.6b00586. Epub 2016 Sep 19.
Polymers conjugated to cyclic peptides capable of forming strong hydrogen bonds can self-assemble into supramolecular bottlebrushes even in aqueous solutions. However, controlling the aggregation of these supramolecular assemblies remains an obstacle that is yet to be overcome. By introducing pH-responsive poly(dimethylamino ethyl methacrylate) (pDMAEMA) arms, the repulsive forces were tuned by adjusting the degree of protonation on the polymer arms. Neutron scattering experiments demonstrated that conjugates in an uncharged state will self-assemble into supramolecular bottlebrushes. Reducing the pH in the system led to a decrease in the number of aggregation, which was reversible by addition of base. Potentiometric titration showed a correlation between the number of aggregation and the degree of ionization of the pDMAEMA arms. Hence, a balance between the strength of the hydrogen bonds and the repulsive electrostatic interactions determines the number of aggregation and extent of self-assembly. The presented work demonstrates that conjugate self-association can be controlled by tuning the charge density on the conjugated polymer arms, paving the way for the use of responsive cyclic peptide conjugates in pharmaceutical applications.
与能够形成强氢键的环肽共轭的聚合物即使在水溶液中也能自组装成超分子瓶刷。然而，控制这些超分子聚集体的聚集仍然是一个有待克服的障碍。通过引入pH响应性聚（甲基丙烯酸二甲氨基乙酯）（pDMAEMA）臂，通过调节聚合物臂上的质子化程度来调节排斥力。中子散射实验表明，处于不带电状态的共轭物将自组装成超分子瓶刷。降低体系的pH值会导致聚集数减少，通过加入碱可使其逆转。电位滴定表明聚集数与pDMAEMA臂的电离程度之间存在相关性。因此，氢键强度与排斥性静电相互作用之间的平衡决定了聚集数和自组装程度。所展示的工作表明，共轭物的自缔合可以通过调节共轭聚合物臂上的电荷密度来控制，这为响应性环肽共轭物在药物应用中的使用铺平了道路。
