Effect of serine residue on the effectiveness of cationic polypeptide-based gene delivery.
Poly-L-lysine(pL) was chemically modified based on two essential features which we recently reported and subjected to the gene-transfer experiment in vitro. Introduction of 25 mol% serine residue to pL slightly enhanced the gene expression level, while trimethylation of epsilon-ammonium groups of lysine did not. Only when pL was modified in both way, giving N2-trimethyl poly(lysine-co-serine), markedly enhanced gene expression was observed. The cellular uptake and localization of DNA in the cells were similar for each cationic polypeptide. DNA forming complex with the polypeptides containing serine residue was found to be well transcribed in in vitro transcription/translation system, suggesting the hydrophilic nature may allow polypeptide/DNA complexes to be recognized by the transcriptional factors and lead the subsequent effective gene expression.
Kimura
T
T
Department of Polymer Science and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Yamaoka
T
T
Iwase
R
R
Murakami
A
A
D000818:Animals; D019556:COS Cells; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D015870:Gene Expression; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000235:genetics; D009997:Osmotic Pressure; D010455:Peptides / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D011107:Polylysine / Q000737:chemistry*; D011994:Recombinant Proteins / Q000235:genetics; D012694:Serine / Q000737:chemistry*; D014162:Transfection
D004274:DNA, Recombinant; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D008156:Luciferases; D008164:Luminescent Proteins; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011073:Polyamines; D000071228:Polyelectrolytes; D011107:Polylysine; D011994:Recombinant Proteins; D012694:Serine; C027794:polyserine