title: 6-Amino-6-deoxy-chitosan. Sequential chemical modifications at the C-6 positions of N-phthaloyl-chitosan and evaluation as a gene carrier.
abstract: The C-6 positions of chitosan were successively modified in a highly regioselective manner. The starting material, N-phthaloyl-chitosan, was successfully converted into the corresponding 6-deoxy-6-halo derivatives by reaction with N-halosuccinimides and triphenylphosphine in N-methyl-2-pyrrolidone. The resulting chloride and bromide derivatives were then substituted with azido groups by reaction with sodium azide at 120 and 80 degrees C, respectively. The azido groups were then reduced to amines via formation of the triphenylphosphinimine intermediate followed by hydrolysis using aqueous hydrazine, which also led to the removal of the N-phthaloyl groups at the C-2 positions. This sequence gave 6-amino-6-deoxy-chitosan, which, unlike chitosan, is soluble in water at neutral pH. The synthesized 6-amino-6-deoxy-chitosan derivative was evaluated as a gene carrier, and the transfection efficiency for COS-1 cells was shown to be superior to chitosan. In addition, the cytotoxicity was similar to chitosan.
authors.affiliation: Department of Applied and Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sumiyoshi, Osaka 558-8585, Japan. satoh@bioa.eng.osaka-cu.ac.jp
authors.forename: Taku
authors.initials: T
authors.lastname: Satoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kano
authors.forename: Mika
authors.initials: M
authors.lastname: Nakatani
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakairi
authors.forename: Seiji
authors.initials: S
authors.lastname: Shinkai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagasaki
mesh_terms: D000818:Animals; D019556:COS Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018014:Gene Transfer Techniques; D012995:Solubility; D014162:Transfection; D014867:Water / Q000737:chemistry
chemical_list: C517097:6-amino-6-deoxy-chitosan; C483239:N-phthaloylchitosan; D014867:Water; D002686:Chitin; D048271:Chitosan