Crystallographic studies of drug-nucleic acid interactions: Proflavine intercalation between the non-complementary base-pairs of cytidilyl-3′,5′-adenosine

摘要: Abstract In order to get insights into the binding of dyes and mutagens with denatured single-stranded nucleic acids possible implications in frameshift mutagenesis, a 1:1 complex between non-self-complementary dinucleoside monophosphate cytidilyl-3′,5′-adenosine (CpA) proflavine was crystallized. The crystals belong tetragonal space group P42212 cell constants = b 19.38(1) A c 27.10(1) . asymmetric unit contains one CpA, nine water molecules by weight. structure determined using Patterson direct methods refined an R-value 11% 2454 diffractometer intensities. CpA forms selfpaired parallel chain dimer molecule intercalated protonated cytosine-cytosine (C · C) pair neutral adenine-adenine (A A) pair. exhibits right-handed helical twist irregular girth. is doubly hydrogen-bonded through N(6) N(7) sites (C(1′)C(1′) distance: 10.97(2) C triply proton shared N(3) 9.59(2) A). To accommodate intercalating dye, sugars successive nucleotide residues adopt two fundamental conformations (5′ end: 3′-endo, 3′ 2′-endo), backbone adopts torsion angle values that fluctuate within their preferred conformational domains: PO bonds (ω, ω′) characteristic (gauche−-gauche−) conformation, CO (φ, φ′) are both trans domain C(4′)C(5′) (ψ) gauche+ region. bases disposed anti glycosyl angles (χ) correlated puckering mode sugar so cytidine residue C(3′)-endo, low χ (12 dg), adenosine C(2′)-endo, high (84 °). stacks more extensively than Between 42-related units there second which well pairs sandwiching it. Both positionally disordered. each its disordered sites, interactions only sugar-phosphate backbone. total 26 has been characterized fully occupied. These hydration involved intricate network hydrogen dye provide on various modes acids. proflavine-CpA shows intercalation planar drugs can occur non-complementary base-pairs. This result be relevant for understanding strong acridine DNA, RNA, polynucleotides. Also, ability proflayine promote self-pairs adenine cytosine could chemical basis alternative mechanism mutagenesis.