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

Abstract

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

Interactions of 1,12-diamino-4,9-dioxadodecane (OSpm) and Cu(II) ions with pyrimidine and purine nucleotides: Adenosine-5′-monophosphate (AMP) and cytidine-5′-monophosphate (CMP)

“…Biogenic amines stabilise membranes, activate some enzymes and, together with their metabolites, catalyse and control biosynthesis of nucleic acids and proteins [12][13][14]. They act as intracellular signalling proteins, protect RNA against the attack of free radicals, and stabilise the structure of A-DNA and Z-DNA [15][16][17][18][19]. In physiological conditions all biogenic amines occur in the protonated form and as such can interact with the negative fragments of other biomolecules, e.g., with negative phosphate groups or/and with donor endocyclic nitrogen atoms of purine or pyrimidine bases of nucleotides [20][21][22][23][24].…”

Elevated polyamines induce c-MYC overexpression by perturbing quadruplex–WC duplex equilibrium

“…More direct evidences have been obtained by NMR studies, which support the existence of nonspecific electrostatic interactions between DNA backbone and cationic polyamines. These studies also revealed that association of polyamines with B-DNA is weak, whereas their association with the folded quadruplex structure is stronger (43,44). Literature findings suggest that high affinity of polyamines toward non-B-DNA secondary structures is governed by both secondary structure and its base composition (45,46).…”

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

“…Spermine at the very least catalyses solvent exchange of the thymine imino protons either by disrupting the water structure or by minor structural changes within the loops. We observed similar spermine‐induced changes of the imino proton resonances of the loop thymines in [d(G 4 T 4 G 4 )] 2 (Keniry, ).…”

“…Titration of spermine into the TBA solution produced very little change to most of the aptamer non‐exchangeable resonances, which is in accord with previous studies of spermine–DNA complexes (Wemmer et al ., ; Banville et al ., ; Van Dam and Nordenskiöld, ; Keniry, ; Keniry and Owen, ). This is best exemplified by the distinctive aromatic and H1′ regions of the TBA spectrum.…”

“…Molecular dynamics (Korolev et al ., ) and Raman studies (Deng et al ., ) suggest that spermine binds electrostatically to DNA and, although spermine retains a certain degree of mobility, it becomes trapped in long‐lived complexes in regions of high negative electrostatic field. Previously, we proposed that the narrow groove of the [d(G 4 T 4 G 4 )] 2 quadruplex is the probable location for a long‐lived spermine residence site (Keniry, ). The regions of highest negative charge density in the TBA structure are the two narrow grooves capped by TpT loops.…”