Effects of Polyamine Binding on the Stability of DNA i-Motif Structures

Abstract

B-form DNA can adopt alternative structures under conditions such as superhelical duress. Alternative DNA structures are favored when there is asymmetric distribution of guanosine and cytosine on complimentary DNA strands. A guanosine-rich strand can form a four-stranded structure known as a quadruplex (G4). The complimentary cytosine-rich strand can utilize intercalating cytosine–cytosine base pairing to form a four-stranded structure known as the i-motif (iM). Both secondary structures are energetically uphill from double-strand DNA (dsDNA), meaning that additional factors are needed for their formation. Most iMs require slightly acidic conditions for structure stabilization. However, crowding agents such as polyethylene glycols and dextrans can shift the p K a of the iM to near-physiological pH ≈ 7. Nucleic acids have long been known to be bound and stabilized by polyamines such as putrescine, spermidine, and spermine. Polyamines have very high concentrations in cells (0.1–30 mM), and their binding to DNA is driven by electrostatic interactions. Polyamines typically bind in the minor groove of DNA. However, because of the unusual structure of iMs, it was unknown whether polyamines might also bind and stabilize iMs. The study described here was undertaken to analyze polyamine–iM interactions. The thermal stability and pH dependence of iM structures were determined in the presence of polyamines. In contrast to dsDNA, our results suggest that polyamines have considerably weaker interactions with iMs, as demonstrated by the minimal change in iM pH dependence and thermal stability. Our results suggest that polyamines are unlikely to provide a significant source of iM stabilization in vivo.

Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands

“…Besides, the compound 3i had moderate Δ T m values (7.0 °C, Table 1 ). It has been reported that the polyamines could stabilize DNA secondary structures [ 34 , 35 ]. The significantly higher ΔT m values of 3c than the other derivatives promoted us to investigate whether the polyamine side chain (1,5,8,12-tetraazadodecane) of 3c could stabilize Py24 individually.…”

Multigenerational Exposure to Uranium Changes Sperm Metabolome in Rats

“…Uranium also seems to have an effect on polyamine metabolism, involving different metabolites such as spermidine (F0) and L-methionine (F1), spermine and finally arginine (F1, F2) [ 58 ]. Polyamines are involved in many processes which are essential for cell growth, DNA double helix stabilization and cationic transporters [ 59 , 60 , 61 , 62 , 63 ]. For example, arginine is known to be involved in the anti-inflammatory process, but also, in the sperm motility [ 64 ].…”

<p>Nano-Graphene Oxide-supported APTES-Spermine, as Gene Delivery System, for Transfection of pEGFP-p53 into Breast Cancer Cell Lines</p>

“…Lane d in agarose gel electrophoresis and no migration of free DNA indicating that most of the DNA was captured by the nanoparticles because of the high affinity of spermine to the DNA. 20 Indeed, it is known that a strong electrostatic interaction exists between the phosphate groups of DNA and the amino groups of spermine, as well as hydrophobic and hydrogen bonds. 21 Nanoparticles stability and nucleic acid protection are important parameters for efficient nucleic acid delivery.…”