title: Synthesis of PAMAM dendrimer derivatives with enhanced buffering capacity and remarkable gene transfection efficiency.
abstract: In this study, we introduced histidine residues into l-arginine grafted PAMAM G4 dendrimers to enhance proton buffering capacity and evaluated the physicochemical characteristics and transfection efficacies in vitro. The results showed that the synthesized PAMAM G4 derivatives effectively delivered pDNA inside cells and the transfection level improved considerably as the number of histidine residues increased. Grafting histidine residues into the established polymer vector PAMAM G4-arginine improved their proton buffering capacity. The cytotoxicity of PAMAM G4 derivatives was tested and it was confirmed that they displayed relatively lower cytotoxicity compared to PEI25KD in various cell lines. Also, confocal microscopy results revealed that PAMAM G4 derivatives effectively delivered pDNA into cells, particularly into the nucleus. These PAMAM dendrimer derivatives conjugated with histidines and arginines may provide a promising polymeric gene carrier system.
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea.
authors.forename: Gwang Sig
authors.initials: GS
authors.lastname: Yu
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Bae
authors.forename: Hye
authors.initials: H
authors.lastname: Choi
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kong
authors.forename: Insung S
authors.initials: IS
authors.lastname: Choi
authors.forename: Joon Sig
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000818:Animals; D002047:Buprenorphine / Q000031:analogs & derivatives; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
chemical_list: C557645:2-(N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl)-3,3-dimethylpentan-2-ol; D050091:Dendrimers; D009757:Nylons; C520550:PAMAM-G4; D002047:Buprenorphine; D004247:DNA