The first derivative of a function of circular dichroism spectra: biophysical study of human telomeric G-quadruplex

Abstract

Depending on conditions and base modifications, telomeric repeats can form many topological structures; parallel, antiparallel and hybrid forms. The influence of salts and some specific ligands on conformational changes has already been established. In this study, we analyze the human telomeric repeats 5'-GGG(TTAGGG)(3)-3' because this sequence forms topologically different structures under various conditions which have been well described by many authors. CD results are compared with electrophoretic and UV absorption spectroscopy results obtained under corresponding conditions in the presence of different ratios of sodium and potassium ions and polyethylene glycol (PEG). We confirmed that the most stable G-quadruplexes could only form under crowding conditions with PEG-200 and K(+) ion, but the molecularity is increased. Other monovalent ions without the presence of K(+) are unable to form the parallel quadruplex conformer and no change of stoichiometry is observed, even when PEG-200 is present. The first derivative of a function applied to CD spectra seems to be a powerful tool for spectra evaluation of any G-quadruplex, and could be more unambiguous than a direct analysis of original spectra.

Kinetic Partitioning Modulates Human Telomere DNA G-Quadruplex Structural Polymorphism

“…A CD spectrum taken on Tel23 molecules prepared by KCl thermal annealing exhibited a positive peak at ~290 nm, a shoulder at ~265 nm, and a small negative peak at ~240 nm (Figure 5A, open circles). These CD signatures indicate a mixture of telomere DNA GQ topologies including anti-parallel, hybrid and parallel conformations, consistent with NMR studies of Tel23 molecules [34,35]. Our smFRET measurements of Tel23 prepared by KCl thermal annealing revealed the presence of at least two distinct FRET states.…”

Molecular dynamics simulations of G-DNA and perspectives on the simulation of nucleic acid structures

“…7). However, this is hypothetical and controversial, albeit supported by some recent experimental work [163]. Therefore, rather than trying to unveil the truth solely by computational techniques, we are more wiling to work for the experimental scientists, providing them with more adjunct information and alternative perspectives.…”

Studying the effect of crowding and dehydration on DNA G-quadruplexes

“…Reversibility of the melting processes can be verified by comparing heating and cooling profiles and/or by changing the heating/cooling rates [29]. (6) Since crowding greatly favors molecular association, unimolecular quadruplex-forming nucleotide sequences under dilute conditions could form G-quadruplexes of higher molecularity under molecular crowding conditions [30,31].…”