6-Amino-6-deoxy-chitosan. Sequential chemical modifications at the C-6 positions of N-phthaloyl-chitosan and evaluation as a gene carrier.
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.
Satoh
Taku
T
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
Kano
Hiroshi
H
Nakatani
Mika
M
Sakairi
Nobuo
N
Shinkai
Seiji
S
Nagasaki
Takeshi
T
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
C517097:6-amino-6-deoxy-chitosan; C483239:N-phthaloylchitosan; D014867:Water; D002686:Chitin; D048271:Chitosan