Nucleotide conformational change induced by cationic bilayers.
The effects of cetyltrimethylammonium bromide (CTAB) micelles and dioctadecyldimethylammonium bromide (DODAB) bilayers on molecular conformation of 2'-deoxyadenosine 5'-monophosphate (dAMP) were evaluated from circular dichroism spectroscopy (CD) and molecular modeling of dAMP conformations of minimal energy upon varying torsion angles for the glycosidic bond (t(1)) for four different conditions of dielectric constant of the medium (E) and negative charge on the phosphate moiety (C), namely, E80_C2, E80_C0, E1_C2, and E1_C0. Upon decreasing medium polarity, a decreased intensity of the negative band over the 190-210 nm region for the dAMP CD spectrum was observed. Upon increasing relative proportion dAMP: DODAB, an increased intensity of the positive band over the 210-230 nm region plus a red shift were obtained that could be attributed to an increased nitrogenous base stacking, similar to A stacking in poly(A). Concomitant base stacking and insertion in the cationic aggregates were observed for DODAB bilayers but not for CTAB micelles. Thereby, the nucleotide extended, anti conformation in pure water typical for nucleotides in DNA was forced by the cationic bilayer to become syn. dAMP conformational modeling upon simultaneous changes in the nucleotide environment (from water to a hydrocarbon phase) and in the charge on phosphate moiety (-2 to zero) allowed to simulate dAMP conformation in the cationic bilayer/dAMP complex. Modeling confirmed the dAMP anti-to-syn conformational change experimentally characterized from CD spectroscopy. This nucleotide conformational change would possibly be at the root of DNA denaturation upon complexation with cationic lipids.
Nantes
Iseli L
IL
Centro Interdisciplinar de Investigação Bioqui;mica, CIIB, Universidade de Mogi das Cruzes, SP, Mogi das Cruzes, Brazil.
Correia
Felipe M
FM
Faljoni-Alario
Adelaide
A
Kawanami
Annelies E
AE
Ishiki
Hamilton M
HM
Amaral
Antonia T-do
AT
Carmona-Ribeiro
Ana M
AM
D002412:Cations / Q000737:chemistry*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D002942:Circular Dichroism; D003838:Deoxyadenine Nucleotides / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
D002412:Cations; D002593:Cetrimonium Compounds; D003838:Deoxyadenine Nucleotides; D008051:Lipid Bilayers; D008823:Micelles; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C015831:dimethyldioctadecylammonium; C012873:2'-deoxy-5'-adenosine monophosphate; D000077286:Cetrimonium