Laboratory of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, Switzerland.
Int J Pharm. 2009 Nov 3;381(2):97-105. doi: 10.1016/j.ijpharm.2009.03.039. Epub 2009 Apr 8.
The objective of this study was to provide a new water-soluble chitosan derivative being functionalized with a Toll-like receptor-2 (TLR-2) agonist. At first, we synthesized the water-soluble TLR-2 agonist omega-amido-[N(alpha)-palmitoyl-oxy-S-[2,3-bis(palmitoyl-oxy)-(2R)-propyl]-[R]-cysteinyl]-alpha-amino poly(ethylene glycol) (Pam(3)Cys-PEG-NH(2)), which was characterized by (1)H and (13)C NMR as well as mass spectroscopy. Secondly, Pam(3)Cys-PEG-NH(2) was then successfully grafted to 6-O-carboxymethyl-N,N,N-trimethyl chitosan polymers (CM-TMC) using EDC/NHS as condensing agents. The copolymer was analysed by means of (1)H and (13)C NMR and FTIR spectroscopy. (13)C NMR spectroscopy did not deliver evidence that an amide bond was formed between CM-TMC and Pam(3)Cys-PEG-NH(2). However, (1)H NMR and FTIR spectroscopy demonstrated clearly that successful grafting took place. Based upon these results, this new TLR-2 functionalized biopolymer merits further investigations as material for vaccine delivery systems.
本研究的目的是提供一种新的水溶性壳聚糖衍生物，其具有 Toll 样受体-2（TLR-2）激动剂的功能。首先，我们合成了水溶性 TLR-2 激动剂 ω-酰胺-[N(α)-棕榈酰氧基-S-[2,3-双（棕榈酰氧基）-（2R）-丙基]-[R]-半胱氨酸基]-α-氨基聚（乙二醇）（Pam(3)Cys-PEG-NH(2)），其通过（1）H 和（13）C NMR 以及质谱进行了表征。其次，使用 EDC/NHS 作为缩合剂，成功地将 Pam(3)Cys-PEG-NH(2)接枝到 6-O-羧甲基-N,N,N-三甲基壳聚糖聚合物（CM-TMC）上。通过（1）H 和（13）C NMR 以及傅里叶变换红外光谱（FTIR）对共聚物进行了分析。（13）C NMR 光谱并未提供 CM-TMC 和 Pam(3)Cys-PEG-NH(2)之间形成酰胺键的证据。然而，（1）H NMR 和 FTIR 光谱清楚地表明接枝成功发生。基于这些结果，这种新的 TLR-2 功能化生物聚合物作为疫苗递送系统的材料值得进一步研究。
