Linhardt Anne, König Michael, Schöfberger Wolfgang, Brüggemann Oliver, Andrianov Alexander K, Teasdale Ian
Institute of Polymer Chemistry, Johannes Kepler University Linz (JKU), Altenberger Straße 69, A-4040 Linz, Austria.
Institute of Organic Chemistry, Johannes Kepler University Linz (JKU), Altenberger Straße 69, A-4040 Linz, Austria.
Polymers (Basel). 2016 Apr 22;8(4):161. doi: 10.3390/polym8040161.
A novel series of peptide based hybrid polymers designed to undergo enzymatic degradation is presented, via macrosubstitution of a polyphosphazene backbone with the tetrapeptide Gly-Phe-Leu-Gly. Further co-substitution of the hybrid polymers with hydrophilic polyalkylene oxide Jeffamine M-1000 leads to water soluble and biodegradable hybrid polymers. Detailed degradation studies, via P NMR spectroscopy, dynamic light scattering and field flow fractionation show the polymers degrade via a combination of enzymatic, as well as hydrolytic pathways. The peptide sequence was chosen due to its known property to undergo lysosomal degradation; hence, these degradable, water soluble polymers could be of significant interest for the use as polymer therapeutics. In this context, we investigated conjugation of the immune response modifier imiquimod to the polymers via the tetrapeptide and report the self-assembly behavior of the conjugate, as well as its enzymatically triggered drug release behavior.
本文介绍了一系列新型的基于肽的杂化聚合物，这些聚合物通过用四肽甘氨酸-苯丙氨酸-亮氨酸-甘氨酸对聚磷腈主链进行宏观取代而设计，旨在进行酶促降解。用亲水性聚环氧烷Jeffamine M-1000对杂化聚合物进行进一步的共取代，得到了水溶性和可生物降解的杂化聚合物。通过磷核磁共振光谱、动态光散射和场流分级进行的详细降解研究表明，这些聚合物通过酶促和水解途径相结合的方式降解。选择该肽序列是因为其已知的可进行溶酶体降解的特性；因此，这些可降解的水溶性聚合物作为聚合物治疗剂可能具有重大意义。在这种情况下，我们研究了免疫反应调节剂咪喹莫德通过四肽与聚合物的缀合，并报告了缀合物的自组装行为及其酶触发的药物释放行为。
