Abstract：
: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.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Nayvelt I,Hyvönen MT,Alhonen L,Pandya I,Thomas T,Khomutov AR,Vepsäläinen J,Patel R,Keinänen TA,Thomas TJdoi
10.1021/bm900958csubject
Has Abstractpub_date
2010-01-11 00:00:00pages
97-105issue
1eissn
1525-7797issn
1526-4602journal_volume
11pub_type
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