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-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.
Laboratory of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, Switzerland.
S
S
Heuking
A
A
Iannitelli
A
A
Di Stefano
G
G
Borchard
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000627:therapeutic use; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D018928:Immunity, Mucosal; D008024:Ligands; D008745:Methylation; D015394:Molecular Structure; D009092:Mucous Membrane; D019906:Nuclear Magnetic Resonance, Biomolecular; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology; D014611:Vaccination / Q000379:methods*
C546859:6-O-carboxymethyl-N,N,N-trimethyl chitosan; D001672:Biocompatible Materials; D004337:Drug Carriers; D008024:Ligands; C118071:N-trimethyl chitosan chloride; D011108:Polymers; D051195:Toll-Like Receptor 2; C546858:omega-amido-(Nalpha-palmitoyloxy-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl)-alpha-amino poly(ethylene glycol); D011092:Polyethylene Glycols; D048271:Chitosan; D003545:Cysteine