Effective control of the intrinsic DNA morphology by photosensitive polyamines

Abstract

Non-viral vectors for gene therapy such as DNA-cationic probe complexes offer important bio-safety advantages over viral approaches, due to their reduced pathogenicity, immunogenicity and cytotoxicity. In the present study we examine two polycationic water-soluble azobenzene derivatives (bis-Azo-2N and bis-Azo-3N) containing different linear unsubstituted polyamine moieties and we demonstrate the ability of such photochromes to destabilize the intrinsic B-DNA secondary structure in a concentration-dependent manner. Furthermore, through a detailed series of biophysical experiments, varying the photochrome conformation, temperature, salt and DNA concentration, we provide a detailed insight into the azobenzene–DNA binding pathway (K_a: bis-Azo-2N(trans)-DNA = 5.3 ± 0.3 × 10⁴ M⁻¹, K_a: bis-Azo-2N(cis)-DNA = 2.6 ± 0.2 × 10⁴ M⁻¹, K_a: bis-Azo-3N(trans)-DNA = 7.1 ± 0.4 × 10⁴ M⁻¹ and K_a: bis-Azo-3N(cis)-DNA = 5.1 ± 0.4 × 10⁴ M⁻¹) establishing the versatility of such materials as promising candidates for use in non-viral gene delivery systems.