Spermine-DNA interactions: a theoretical study.

Abstract

Models for the interaction of spermine and DNA were studied by performing conformational energy calculations on spermine and molecular mechanics calculations on major and minor groove complexes of spermine and oligomers of DNA. Docked into the major groove of B-DNA, spermine stabilizes the complex by aimig interactions between proton acceptors on the oligomer and proton donors on spermine. This is achieved by bending the major groove of DNA over spermine and altering oligomer sugar puckering and interstrand phosphate distances. By comparison, Liquori's minor groove model appears to be less stable than the major groove model. This evidence favors a preferential binding of spermine to certain sites in DNA, which provides a powerful force for the modification of DNA conformation.Polyamines are aliphatic polycationic compounds that are found in all cells and have a significant role in the regulation of normal and malignant cell proliferation (1). Polyamine biosynthesis is highly regulated, and intracellular levels of polyamines can change rapidly by orders of magnitude when cell growth is stimulated (1). It has been proposed that polyamines affect growth by interacting with DNA. Evidence for these interactions obtained from experiments conducted in cell-free systems includes the ability of polyamines to precipitate DNA (2) and to raise the melting temperature of natural DNAs (3). Other results obtained by electron microscopy and micrococcal nuclease digestion of DNA show that polyamines can produce an organized condensed DNA structure (4). On the cellular level, depletion of intracellular polyamines by treatment with inhibitors of polyamine biosynthesis produces effects consistent with models in which polyamine interactions alter DNA conformation (5).It has been shown recently that polyamines can cause a B to Z conformational transition in both poly[d(G-m5C)] and poly[d(G-C)] (6, 7). In these studies, significant and specific changes in DNA structure can take place at low polyamine/ base-pair ratios. Differences in the ability of two spermidine analogs with the same charge but different structures to cause the B to Z transition suggest that a specific interaction causes the transition (8).Even though the interactions between DNA and polyamines have been described in detail, the molecular basis for an interaction has not been well-characterized. A major controversy in the field involves the question of whether or not the interaction is specific. In theoretical studies, polyamines have been treated as point concentrations of positive charge that interact with a DNA molecule considered to be a linear concentration of negative charge (9); in this counterion condensation model, chemical structure is ignored and specificity in interaction is not considered. Experimental results consistent with this model have been published (9)(10)(11). In other models, structures ofboth DNA and polyamines are taken into account. In one of these models, the tetracationic polyamine spermine bridges the minor groove ofDNA to give a ...

Structural Analysis of DNA Interactions with Biogenic Polyamines and Cobalt(III)hexamine Studied by Fourier Transform Infrared and Capillary Electrophoresis

“…Feuerstein et al (45) found that spermine prefers the major groove of B-DNA followed by minor groove interaction with phosphate binding being the least favorable. Different theoretical studies (46,47) agreed with this hypothesis of spermine cation interacting with the dsDNA bases across the major groove. However, recent molecular mechanics simulation studies (48 -50) found that spermine occupies more varied sites, including binding along the backbone and bridging both the major and minor grooves.…”

“…Spermine interaction with the bases at the major groove was demonstrated by x-ray studies performed on spermine-oligonucleotide complexes (21,42). In addition, the interaction between spermine and DNA has been widely studied using theoretical calculations (45,47). These studies indicated that the interaction at the major groove of alternating purine/pyrimidine sequences appears to be the most favorable of all models presented and is associated with significant bending of DNA.…”

Inversion of DNA charge by a positive polymer via fractionalization of the polymer charge

“…The only requirements for flexibility of tails assumed in our calculation is that the tail can be raised in such a way that its end monomer avoids the end monomer the neighboring PE molecule. This requirements is fulfilled in many cases, for example, for the spermine 19 (Z = 4). (One should take into account that the neighboring PE charged monomers are usually connected by a chain of several neutral monomers).…”

Effect of food components and processing parameters on DNA degradation in food

“…The amines putrescine and spermine exhibited protective effects at concentrations of ≥1 mM and ≥0.5 mM, equal to 0.09 g.kg -1 and 0.101 g.kg -1 , respectively. Spermine is a key component in the cell proliferation process (Heby, 1981), and when docked into the major groove of B-DNA, stabilizes the complex by maximizing interactions between proton acceptors on DNA and proton donors on spermine (Feuerstein et al, 1986). Deng et al (2000) demonstrated the capability of spermine and spermidine to bind and condense B-DNA without disrupting the native structure.…”