DNA condensation by chiral α-methylated polyamine analogues and protection of cellular DNA from oxidative damage

Irina Nayvelt, Mervi T. Hyvönen, Leena Alhonen, Ipsit Pandya, Thresia Thomas, Alex R. Khomutov, Jouko Vepsäläinen, Rajesh Patel, Tuomo A. Keinänen, T. J. Thomas

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Polyamines are essential molecules supporting the structure, conformation, and function of nucleic acids and proteins. We studied stereoisomers of α,α?-dimethylated spermine [(R,R)-Me2Spm, (S,S)-Me 2Spm, (R,S)-Me2Spm] for their ability to provoke DNA condensation and protect DNA from damage. (R,R)- and (R,S)-Me2Spm displayed more efficient condensing ability than spermine, with significantly lower EC50 (concentration for 50% compaction) values (p ≤ 0.01). However, spermine exerted slightly more duplex stabilization than Me 2Spm. 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 Me2Spm 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 Me2Spm 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.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalBiomacromolecules
Volume11
Issue number1
DOIs
StatePublished - Jan 11 2010

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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