title: Synthesis of a new conjugated polymer for DNA alkylation and gene regulation.
abstract: A new polyfluorene derivative containing pendent alkylating chlorambucil (PFP-Cbl) was synthesized and characterized. Under direct incubation with DNA in vitro, PFP-Cbl could undergo an efficient DNA alkylating reaction and induce DNA cross-linking. In vitro transcription and translation experiment exhibited that the PFP-Cbl significantly down-regulated the gene expression of luciferase reporter plasmid. The down-regulation of gene expression was also verified through the transfection experiment of p-EGFP plasmid, which showed decreased green fluorescent protein (GFP) in cells. Meanwhile, the self-luminous property of PFP-Cbl could make it able to trace the internalized PFP-Cbl and plasmid complexes resulted from cross-linking in cells by fluorescent microscopy. Combining the features of alkylating function, multivalent binding sites, and fluorescent characteristics, PFP-Cbl provides a new insight in the area of gene regulation and extends the new applications of conjugated polymers (CPs).
authors.affiliation: Beijing National Laboratory for Molecular Science, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, P R China.
authors.forename: Chenyao
authors.initials: C
authors.lastname: Nie
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhu
authors.forename: Liheng
authors.initials: L
authors.lastname: Feng
authors.forename: Fengting
authors.initials: F
authors.lastname: Lv
authors.forename: Libing
authors.initials: L
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000478:Alkylation; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis; D001665:Binding Sites / Q000235:genetics; D002699:Chlorambucil / Q000138:chemical synthesis; D003432:Cross-Linking Reagents / Q000138:chemical synthesis; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D011108:Polymers / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003432:Cross-Linking Reagents; D011108:Polymers; D049452:Green Fluorescent Proteins; D002699:Chlorambucil; D004247:DNA