A facile synthesis and physical properties of nano-sized dendritic alpha,epsilon-poly(L-lysine)s for the delivery of nucleic acids.
A series of nano-sized dendritic alpha,epsilon-poly(L-lysine)s (DPL) were synthesized by the solid-phase peptide synthesis method, using a core epsilon-peptide structure consisting of eight lysine residues. Surface amines of dendritic alpha,epsilon-poly(L-lysine) were characterized by comparing the retention times of a reverse phase HPLC with the electrophoretic mobilities of capillary zone electrophoresis (CZE) and non-denatured polyacrylamide gel electrophoresis (PAGE). The elution times of alpha,epsilon-poly(Llysine) in HPLC were well correlated with the electrophoretic mobilities of CZE and PAGE. The separation was dependent on size, shape of molecule and the number of surface amine. The alpha,epsilon-poly(L-lysine) formed a complex with nucleic acids at various charge ratios and the degree of complex formation was size- and structure-dependent. Atomic force microscopy of the complex visualized the size and morphology of alpha,epsilon-poly(L-lysine)/DNA complex as a nano-sized spherical shape. The small size in complex formation provides a promise for in vivo therapeutic application of dendritic alpha,epsilon-poly(L-lysine)s or their derivatives in the delivery of gene or oligonucleotide.
Eom
Khee Dong
KD
Department of Pharmacology and Dental Therapeutics, College of Dentistry, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Korea.
Kim
Jin Sook
JS
Park
Sun Mi
SM
Kim
Myong Soo
MS
Yu
Rina
R
Jung
Hae Man
HM
Kim
Saeng Gon
SG
Yoo
Hoon
H
D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers; D003712:Dendrites / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D019075:Electrophoresis, Capillary; D004591:Electrophoresis, Polyacrylamide Gel; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D053761:Nanocomposites / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D050091:Dendrimers; D009696:Nucleic Acids; C104700:PAMAM Starburst; D010455:Peptides; D011073:Polyamines; D011107:Polylysine