A phosphorus NMR study of the reaction products of cis-diamminedichloroplatinum (II) with a double-helical oligonucleotide and with DNA

AbstractThe structural distortion of oligonucleotides upon cis-PtCl2(NH3)2{d(T-C-T-C-G-G-T-C-T'-C-N7(5) N7(6)} reveals shifting of 4 phosphorus resonances due to platination. 3 Resonances could be assigned by selective 31P-irradiation, showing P(6) (P between the two Gs) to be shifted 1.5 ppm to low field. In the concomitant double strands P(6) is shifted 0.9 ppm to lower field. A similar peak has been observed in platinated salmon sperm DNA (37°C), indicating that Pt-binding to GpG-fragments in DNA is similar to that found for the decanucleotide, so the distortion of DNA might be comparable

Cyclic diguanylic acid behaves as a host molecule for planar intercalators

AbstractCyclic ribodiguanylic acid, c-(GpGp), is the endogenous effector regulator of cellulose synthase. Its three-dimensional structure from two different crystal forms (tetragonal and trigonal) has been determined by X-ray diffraction analysis at 1 Å resolution. In both crystal forms, two independent c-(GpGp) molecules associate with each other to form a self-intercalated dimer. A hydrated cobalt ion is found to coordinate to two N7 atoms of adjacent guanines, forcing these two guanines to destack with a large dihedral angle (32°), in the dimer of the tetragonal form. This metal coordination mechanism may be relevant to that of the anticancer drug cisplatin. Moreover, c-(GpGp) exhibits unusual spectral properties not seen in any other cyclic dinucleotide. It interacts with planar organic intercalator molecules in ways similar to double helical DNA. We propose a cage-like model consisting of a tetrameric c-(GpGp) aggregate in which a large cavity (‘host’) is generated to afford a binding site for certain planar intercalators (‘guests’)

Three-dimensional crystal structure of the A-tract DNA dodecamer d(CGCAAATTTGCG) complexed with the minor-groove-binding drug Hoechst 33258

6 pages, 5 figures, 2 tables.-- PMID: 7517864 [PubMed].-- Available online Mar 3, 2005.The molecular structure of the DNA A-tract dodecamer d(CGCAAATTTGCG) complexed with the drug Hoechst 33258 has been determined by X-ray diffraction analysis. The Hoechst molecule binds in the DNA minor groove covering the sequence AATTT of the central A-tract, with the piperazine group close to one of the GC regions. The drug molecule makes two three-centered hydrogen bonds from the nitrogen atoms of the benzimidazole rings to the N3 and O2 atoms of the DNA bases. Although a high propeller twist is observed in the A-tract, only one unsymmetrical three-centered hydrogen bond is present in the DNA major groove. The structure is compared with other minor-groove-binding drug complexes and the influence of these drugs on DNA A-tracts is discussed.This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (SAL90-0824), the Dirección General de Investigación Cientíca y Técnica (PB92-0117) and the Centre de Supercomputació de Catalunya to M. Coll. M. C. V. acknowledges a fellowship from the Generalitat de Catalunya. I. G.- S. acknowledges a Ministerio de Educacidn y Ciencia fellowship.Peer reviewe

The modified DNA base β-D-glucosylhydroxymethyluracil confers resistance to micrococcal nuclease and is incompletely recovered by 32P- postlabeling

The hypermodified DNA base β-D-glucosylhydroxy-methyluracil, also called J, is a naturally occurring DNA modification. J was initially detected by 32P-postlabeling in Trypanosoma brucei and was recently also found in several other eukaryotic parasites. To use 32P-postlabeling as a method to quantitate the absolute levels of J in DNA we have tested the postlabeling efficiency of J using various synthesized standard oligonucleotides containing J. It is known that modified nucleotides, especially bulky ones, are often partially recovered by postlabeling and they are poor substrates for some of the enzymes used. We found that on average only 50% of J is recovered, which shows that the amount of J in T. brucei DNA has been twofold underestimated. Experiments with a short oligomer and defined pyrimidine tracts showed that the incomplete recovery of J is caused at least in part by resistance of J-containing DNA to degradation by micrococcal nuclease