Dendritic oligoguanidines as intracellular translocators.
A series of polyguanidylated dendritic structures that can be used as molecular translocators have been designed and synthesized based on nonpeptide units. The dendritic oligoguanidines conjugated with fluorescein or with a green fluorescent protein (GFP) mutant as cargos were isolated and characterized. Quantification and time-course analyses of the cellular uptake of the conjugates using HeLa S3 and human cervical carcinoma cells reveal that the polyguanidylated dendrimers have comparable translocation efficiency to the Tat(49-57) peptide. Furthermore, the deconvolution microscopy image analysis shows that they are located inside the cells. These results clearly show that nonlinear, branched dendritic oligoguanidines are capable of translocation through the cell membrane. This work also demonstrates the potential of these nonpeptidic dendritic oligoguanidines as carriers for intracellular delivery of small molecule drugs, bioactive peptides, and proteins.
LG Biomedical Institute, 3252 Holliday Court, Suite 101, La Jolla, CA 92037, USA.
Hyun-Ho
HH
Chung
Guido
G
Harms
Churl Min
CM
Seong
Byung Hyune
BH
Choi
Changhee
C
Min
Joseph P
JP
Taulane
Murray
M
Goodman
D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D019793:Fluorescein / Q000737:chemistry; D049452:Green Fluorescent Proteins; D006146:Guanidines / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D021381:Protein Transport
D001704:Biopolymers; D006146:Guanidines; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D019793:Fluorescein