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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 32, Number 2
BKCSDE 32(2)
February 20, 2011 


Sequential Conjugation of 6-Aminohexanoic Acids and L-Arginines to Poly(amidoamine) Dendrimer to Modify Hydrophobicity and Flexibility of the Polymeric Gene Carrier

Gwang Sig Yu, Ha Na Yu, Yun Hui Choe, Sang Jae Son, Tai Hwan Ha*, Joon Sig Choi*
Dendrimer, Gene delivery, Polyplex, Transfection
We synthesized a novel cationic dendrimer consisting of a poly(amidoamine) dendrimer (PAMAM, generation 4) backbone with both L-arginine (Arg) at the termini and 6-aminohexanoic acid (Ahx) between the original core polymer and the peripheral Arg units. The sequential chemical modification of PAMAM G4 with Ahx and Arg resulted in higher transfection efficiency with much less cytotoxicity. PAMAM G4-Ahx-Arg formed stable polyplexes at weight ratios of 8:1 or higher (polymer: plasmid DNA), and the mean polyplex diameter was 180 ± 20 nm. PAMAM G4-Ahx- Arg showed much higher transfection ability than PAMAM G4 or PAMAM G4-Ahx. Furthermore, PAMAM G4- Ahx-Arg was much less cytotoxic than PEI25KD and PAMAM G4-Arg. In addition to Arg grafting of the PAMAM dendrimer, which endows a higher transfection capability, the addition of Ahx spacer increased dendrimer hydrophobicity, introduced flexibility into the conjugated amino acids, and reduced cytotoxicity. Overall, it appears that the concomitant modification of PAMAM with Ahx and Arg could lead to new PAMAM conjugates with better performances.
651 - 655
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