DNA condensation by chiral alpha-methylated polyamine analogues and protection of cellular DNA from oxidative damage.
Polyamines are essential molecules supporting the structure, conformation, and function of nucleic acids and proteins. We studied stereoisomers of alpha,alpha'-dimethylated spermine [(R,R)-Me(2)Spm, (S,S)-Me(2)Spm, (R,S)-Me(2)Spm] for their ability to provoke DNA condensation and protect DNA from damage. (R,R)- and (R,S)-Me(2)Spm displayed more efficient condensing ability than spermine, with significantly lower EC(50) (concentration for 50% compaction) values (p < or = 0.01). However, spermine exerted slightly more duplex stabilization than Me(2)Spm. Condensation resulted in nanoparticles with hydrodynamic radii between 39.6 and 48.4 nm, and electron microscopy showed the presence of toroids and spheroids. Natural polyamines and stereoisomers of Me(2)Spm protected DNA against DNase digestion and oxidative stress in vitro and against etoposide and oxidative stress in DU145 cells but afforded little protection against UV-C irradiation. Our findings indicate that Me(2)Spm stereoisomers are efficient DNA packaging agents with potential applications in gene delivery. Our study also reveals stereospecificity in DNA interaction and protection against cellular stress.
Nayvelt
Irina
I
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Hyvönen
Mervi T
MT
Alhonen
Leena
L
Pandya
Ipsit
I
Thomas
Thresia
T
Khomutov
Alex R
AR
Vepsäläinen
Jouko
J
Patel
Rajesh
R
Keinänen
Tuomo A
TA
Thomas
T J
TJ
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects*; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008745:Methylation; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D013096:Spermine; D004247:DNA; C427203:calf thymus DNA