Macro-branched cell-penetrating peptide design for gene delivery.
Many kinds of macromolecular compounds that comprise a series of branches around an inner core have been made and showed some promises as DNA- and drug-delivery systems. In this study, a method for peptide polymer design having macro-branched peptide structure was adapted and it was applied for plasmid DNA delivery for the first time; acryloyl chloride was used by introducing the double bond into the N-terminal of HIV-1 tat (47-57, YGRKKRRQRRR). After being cleaved from resin, it was transformed to a polymer which possesses a poly-propionyl core matrix with tat branches and was named polytat by radical polymerization. After further separation and purification by Sephadex G150, polytat P1, polytat P2 and polytat P3 were acquired and the average molecular weight of the different macromolecules are 240, 178 and 82 kDa. We found that all these compounds complexed with plasmid DNA and showed significant transfection capabilities in a variety of mammalian cell lines, but acrylyl-tat or tat alone showed no significant transfection capability. Further study showed that polytat could be applied for plasmid DNA delivery for cell lines even with serum by endocytosis-mediated pathways.
Liu
Zhihui
Z
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, People's Republic of China.
Li
Moyi
M
Cui
Dafu
D
Fei
Jian
J
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D015696:Gene Products, tat; D010446:Peptide Fragments