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- W2050657910 abstract "We have reported that polylysine substituted with histidyl residues (His) was suited to make complexes with plasmid DNA (pDNA) and to transfect cells in vitro in the presence of serum. The present study was performed to determine whether the acetylation of the α-amino group of histidyl residues (AcHis) had an influence on the size and the charge of polyplexes and on their transfection efficiency. We found that the presence of free α-amino groups allowed the formation of smaller polyplexes but did not modify the ζ potential of +17 mV. At a physiological salt concentration, the adsorption of many serum proteins on His- and AcHis-polyplexes reduced their size below 100 nm, inhibited their aggregation, and reversed their ζ potential to −25 mV. The acetylation of the α-amino groups reduced slightly the adsorption of serum proteins. The presence of the α-amino groups increased the pK of the imidazole protonation of histidine bound to polylysine from pH 5.8 to 6.9; in addition, the protonation was further elevated in the presence of pDNA. Serum stabilized negative histidylated polyplexes were less taken up by cells but their transfection efficiency did not decrease; depending on the cell line, His-polyplexes were more efficient than AcHis-polyplexes. The results indicate that (i) the α-amino groups of histidyl residues bound to polylysine favorably influence the size and the transfection efficiency of polyplexes, (ii) the α-amino groups also elevate the imidazole protonation of His-polyplexes, which is suited to destabilize the membrane of early endocytic vesicles in order to favor pDNA delivery in the cytosol, and (iii) the absorption of selective serum proteins on His-polyplexes could be a way for in vivo gene targeting." @default.
- W2050657910 created "2016-06-24" @default.
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- W2050657910 date "2000-12-21" @default.
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- W2050657910 title "Histidylated Polylysine as DNA Vector: Elevation of the Imidazole Protonation and Reduced Cellular Uptake without Change in the Polyfection Efficiency of Serum Stabilized Negative Polyplexes" @default.
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- W2050657910 doi "https://doi.org/10.1021/bc0000738" @default.
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