Interactions of polyamines with the DNA octamers d(m5CG)4 and d(GGAATTCC): A 1H-NMR investigation

2003

FEBS Letters

The association of [1P P,1Q Q-13 C 2 ]spermine ([1P P,1Q Q-13 C 2 ]-N,NP P-bis(3-aminopropyl)-1,4-butanediamine) with duplex and quadruplex DNA has been studied by nuclear magnetic resonance spectroscopy. 1D NOESY experiments using two-way selective cross-polarization (ISI-SCP-NOESY) showed spermine intramolecular NOEs are either weakly positive or weakly negative when spermine is complexed to duplex B-DNA and linear four-stranded quadruplex DNA. In contrast, large negative intramolecular NOEs are observed when spermine is complexed to two distinct forms of folded quadruplex DNA suggesting greater immobilization of spermine on these folded DNA quadruplexes. No changes in the quadruplex stem structure are observed but there are minor changes to the loop structure of a two-stranded folded quadruplex on binding spermine. ß

Section: Resultssupporting

confidence: 90%

“…No intramolecular nuclear Overhauser effects (NOEs) between spermine and either hexanucleotide were observed. These observations were confirmed by van Dam and Nordenskiöld [14].…”

Section: Introductionsupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

A comparison of the association of spermine with duplex and quadruplex DNA by NMR

2003

FEBS Letters

Insight into the molecular recognition of spermine by DNA quadruplexes from an NMR study of the association of spermine with the thrombin‐binding aptamer

J of Molecular Recognition

Owen

2013

The preferred residence sites and the conformation of DNA-bound polyamines are central to understanding the regulatory roles of polyamines. To this end, we have used a series of selective (13)C-edited and selective total correlation spectroscopy-edited one-dimensional (1D) nuclear Overhauser effect spectroscopy NMR experiments to determine a number of intramolecular (1)H nuclear Overhauser effect (NOE) connectivities in (13)C-labelled spermine bound to the thrombin-binding aptamer. The results provide evidence that the aptamer-bound spermine adopts a conformation that optimizes electrostatic and hydrogen bond contacts with the aptamer backbone. The distance between the nitrogen atoms of the central aminobutyl is reduced by an increase in the population of gauche conformers at the C6-C7 bonds, which results in either a curved or S-shaped spermine conformation. Molecular modelling contributes insight toward the mode of spermine binding of these spermine structures within the narrow grooves of DNA quadruplexes. In each case, the N5 ammonium group makes hydrogen bonds with two nearby phosphates across the narrow groove. Our results have implications for the understanding of chromatin structure and the rational design of quadruplex-binding drugs.

The flanking sequence contributes to the immobilisation of spermine at the G‐quadruplex in the NHE (nuclease hypersensitivity element) III₁ of the c‐Myc promoter

Owen

2014

FEBS Letters

a b s t r a c tDefining the molecular basis of the DNA sequence selectivity of polyamine binding is central to understanding polyamine-dependent gene expression. We have studied, by selective NMR experiments, the variation of spermine mobility and conformation in the presence of G-quadruplexes formed by sequences of the purine-rich strand of the c-Myc promoter, nuclease hypersensitivity element III 1 (NHE III 1 ). All the NHE quadruplexes restrict spermine mobility and induce a spermine conformational change but the most effective immobilisation occurs when all five G-tracts of the NHE III 1 are present. This suggests structure within the nucleotides flanking the G-quadruplex has a role in immobilising spermine.