title: Cyclen Grafted with poly[(Aspartic acid)-co-Lysine]: Preparation, Assembly with Plasmid DNA, and in Vitro Transfection Studies.
abstract: Development of safe and effective gene carriers is the key to the success of gene therapy. Nowadays, it is still required to develop new methods to improve nonviral gene delivery efficiency. Herein, copolymers of poly[(aspartic acid)-co-lysine] grafted with cyclen (cyclen-pAL) were designed and evaluated for efficient gene delivery. Two copolymers with different Asp/Lys block ratios were prepared and characterized by NMR and gel permeation chromatography analysis. Agarose gel retardation, circular dichroism, and fluorescent quenching assays showed the strong DNA-binding and protection ability for the title compounds. Atomic force microscopy studies clearly delineated uniform DNA globules with a diameter around 100 nm, induced by cyclen-pAL. By grafting cyclen on Asp, relatively high gene delivery efficiency and low cytotoxicity of the modified copolymers were achieved compared with their parent compounds. The present work might help to develop strategies for design and modification of polypeptide copolymers, which may also be applied to favorable gene expression and delivery.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Changguo
authors.initials: C
authors.lastname: Du
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Baojing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology , 100029 Beijing, P. R. China.|State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University Health Sciences Center , 100083 Beijing, P. R. China.
authors.forename: Renzhong
authors.initials: R
authors.lastname: Qiao
mesh_terms: D000080027:Cyclams; D004247:DNA / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006571:Heterocyclic Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014162:Transfection
chemical_list: D000080027:Cyclams; D006571:Heterocyclic Compounds; D011108:Polymers; D004247:DNA; C038072:cyclen
keywords: DNA assembly; cyclen; drug delivery; gene therapy; polypeptide; synthesis