Dental School, University of Sheffield , 19 Claremont Crescent, Sheffield, South Yorkshire, U.K. , S10 2TA.
School of Chemistry and Biosciences, University of Bradford , Bradford, West Yorkshire, U.K. , BD1 1DP.
Biomacromolecules. 2017 Sep 11;18(9):2887-2899. doi: 10.1021/acs.biomac.7b00800. Epub 2017 Aug 18.
The behavior of a linear copolymer of N-isopropylacrylamide with pendant vancomycin functionality was compared to an analogous highly branched copolymer with vancomycin functionality at the chain ends. Highly branched poly(N-isopropylacrylamide) modified with vancomycin (HB-PNIPAM-van) was synthesized by functionalization of the HB-PNIPAM, prepared using reversible addition-fragmentation chain transfer polymerization. Linear PNIPAM with pendant vancomycin functionality (L-PNIPAM-van) was synthesized by functionalization of poly(N-isopropylacrylamide-co-vinyl benzoic acid). HB-PNIPAM-van aggregated S. aureus effectively, whereas the L-PNIPAM-van polymer did not. It was found that when the HB-PNIPAM-van was incubated with S. aureus the resultant phase transition provided an increase in the intensity of fluorescence of a solvatochromic dye, nile red, added to the system. In contrast, a significantly lower increase in fluorescence intensity was obtained when L-PNIPAM-van was incubated with S. aureus. These data showed that the degree of desolvation of HB-PNIPAM-van was much greater than the desolvation of the linear version. Using microcalorimetry, it was shown that there were no significant differences in the affinities of the polymer ligands for d-Ala-d-Ala and therefore differences in the interactions with bacteria were associated with changes in the probability of access of the polymer bound ligands to the d-Ala-d-Ala dipeptide. The data support the hypothesis that generation of polymer systems that respond to cellular targets, for applications such as cell targeting, detection of pathogens etc., requires the use of branched polymers with ligands situated at the chain ends.
线性 N-异丙基丙烯酰胺共聚物与侧链万古霉素功能的行为与具有末端万古霉素功能的类似高度支化共聚物进行了比较。通过 HB-PNIPAM 的功能化合成了侧链万古霉素修饰的高度支化聚（N-异丙基丙烯酰胺）（HB-PNIPAM-van），HB-PNIPAM 是通过可逆加成-断裂链转移聚合制备的。通过聚（N-异丙基丙烯酰胺-co-乙烯基苯甲酸）的功能化合成了具有侧链万古霉素功能的线性 PNIPAM（L-PNIPAM-van）。HB-PNIPAM-van 有效地聚集金黄色葡萄球菌，而 L-PNIPAM-van 聚合物则没有。研究发现，当 HB-PNIPAM-van 与金黄色葡萄球菌孵育时，所得的相转变会增加添加到系统中的溶剂变色染料尼罗红的荧光强度。相比之下，当 L-PNIPAM-van 与金黄色葡萄球菌孵育时，荧光强度的增加明显较低。这些数据表明，HB-PNIPAM-van 的去溶剂化程度远大于线性版本的去溶剂化程度。使用微量量热法表明，聚合物配体对 d-Ala-d-Ala 的亲和力没有显着差异，因此与细菌的相互作用的差异与聚合物结合配体进入 d-Ala-d-Ala 二肽的概率的变化有关。该数据支持以下假设：生成响应细胞靶标的聚合物系统，例如细胞靶向、病原体检测等，需要使用具有末端配体的支化聚合物。
