Toll-like receptor-2 agonist functionalized biopolymer for mucosal vaccination

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-NH2), which was characterized by H-1 and C-13 NMR as well as mass spectroscopy. Secondly, Pam(3)Cys-PEG-NH2 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 H-1 and C-13 NMR and FTIR spectroscopy. C-13 NMR spectroscopy did not deliver evidence that an amide bond was formed between CM-TMC and Pam(3)Cys-PEG-NH2. However, H-1 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. (C) 2009 Elsevier B.V. All rights reserved.