DNA compaction by divalent cations: structural specificity revealed by the potentiality of designed quaternary diammonium salts.
DNA interaction with quaternary diammonium dications, R(CH(3))(2)N(+)(CH(2))(n)N(+)(CH(3))(2)R, having various intercharge distances, lengths, and branching, and the chemical nature of the hydrophobic substituents were investigated by fluorescent microscopy and circular dichroism (CD) spectroscopy to reveal their structural specificity for binding to DNA. The conformational behavior of DNA was found to be highly sensitive to the structure of the dications with separated charges. The distance between two ammonium groups greatly influences the compaction activity of the dications. To explain this situation, we proposed a model that demonstrates that the charge density of the dication and the geometric fit between DNA phosphates and the ammonium groups in the dications play an important role in providing efficient DNA collapse. Elongation of the alkyl substituents (R) in the diammonium salts from ethyl to hexyl did not generate any significant alterations in the compaction activities, whereas the branching of substituents caused a drastic decrease in their compaction ability. Based on the results of CD spectroscopy, it was found that the ability of the dications to provoke a DNA transition from the B-form to A-form was also specific: it depended on their intercharge distances and was independent of the length of alkyl substituents.
Graduate School of Environmental Studies and CREST, JST (Japan Science and Technology Agency), c/o School of Informatics and Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Anatoly A
AA
Zinchenko
Vladimir G
VG
Sergeyev
Kuniaki
K
Yamabe
Shizuaki
S
Murata
Kenichi
K
Yoshikawa
D002413:Cations, Divalent / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D015195:Drug Design; D018014:Gene Transfer Techniques; D057927:Hydrophobic and Hydrophilic Interactions; D009690:Nucleic Acid Conformation / Q000187:drug effects; D044367:Phase Transition / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D002413:Cations, Divalent; D000644:Quaternary Ammonium Compounds; D004247:DNA