Effect of glucocorticoids and their complexes with apolipoprotein A‐I on the secondary structure of eukaryotic DNA

The tetrahydrocortisol–apolipoprotein A‐I complex specifically interacts with eukaryotic DNA isolated from rat liver. This interaction is highly cooperative and of a saturating nature. One DNA molecule binds about 54 molecules of the complex. Small‐angle X‐ray scattering has shown that hydrogen bonds between nitrous bases are destroyed and that single‐stranded structures are formed at the interaction of the tetrahydrocortisol–apolipoprotein A‐I complex with eukaryotic DNA. The most probable site of binding the tetrahydrocortisol–apolipoprotein A‐I complex with DNA is the sequence of the CC(GCC)_n type entering the structure of many genes, among them the structure of the human apolipoprotein A‐I gene. Oligonucleotide of this type has been synthesized. The association constant (K_ass) of its complexation was shown to be 1.66 · 10⁶ M^?1. Substitution of tetrahydrocortisol for cortisol in the complex results in a considerable decrease of K_ass. IR‐spectroscopy study has shown that the interaction of tetrahydrocortisol with oligonucleotide CC(GCC)_3–5 is accompanied by the formation of hydrogen bonds via the CO‐NH, PO₂, and OH groups of desoxycytidinephosphate. The tetrahydrocortisol–apolipoprotein A‐I complex alters the DNA secondary structure formed at the interaction with the hormone, causing the structural transition “order → tangle.” It is assumed that in the GC‐pairs of the given DNA sequence, tetrahydrocortisol initiates the rupture of hydrogen bonds, while the hydrophobic interactions between nitrous bases and apoA‐I intensify this process. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005