A multidimensional heteronuclear NMR study has demonstrated that a guanine-rich DNA oligonucleotide originating from the N-myc gene folds into G-quadruplex structures in the presence of K+, NH4+, and Na+ ions. A monomeric G-quadruplex formed in K+ ion containing solution exhibits three G-quartets and flexible propeller-type loops. The 3D structure with three single nucleotide loops represents a missing element in structures of parallel G-quadruplexes. The structural features together with the high temperature stability suggest specific biological role of G-quadruplex formation within the intron of the N-myc gene. An increase in K+ ion and oligonucleotide concentrations resulted in transformation of the monomeric G-quadruplex into a dimeric form. The dimeric G-quadruplex exhibits six stacked G-quartets, parallel strand orientations and propeller-type loops. A link between the third and the fourth G-quartets consists of two adenine residues that are flipped out to facilitate consecutive stacking of six G-quartets.
COBISS.SI-ID: 4920602
DNA oligonucleotide d[G3ATG3ACACAG4ACG3] has been folded into a G-quadruplex in the presence of K+ ions and its high-resolution NMR solution-state structure was determined. Oligonucleotide comprises of four G-tracts with the third one consisting of four guanines. G-tracts are intervened with non-G stretches of different lengths. A single intramolecular antiparallel (3+1) G-quadruplex exhibits three stacked G-quartets connected with propeller, diagonal and edgewise loops of different lengths. The propeller and edgewise loops are well structured, whereas the longer diagonal loop is more flexible. The determined 3D structure represents the first high resolution G-quadruplex structure where all of the three main loop types are present. 1D 1H-NMR spectra in sodium and ammonium ion containing solutions suggested the formation of several structures.
COBISS.SI-ID: 5032474
Nucleic acid sequences containing short tracts of guanine residues are prone to fold into G-quadruplex structures composed of stacking G-quartets. It is well known that quadruplex structures exhibit a remarkable dependency on cations due to the presence of four carbonyl oxygen atoms in the middle of each G-quartet plane. Kinetics of cation movement is intrinsically correlated with structural details and local plasticity of specific G-quadruplex topology. The comparison of the rate constants for 15NH4+ ion movements from G-quadruplex into bulk solution for the studied tetrameric quadruplex structures revealed slower cation movements at the 5’-end of the quadruplexes. Furthermore, the cation movement through an all-syn G-quartet is slower in comparison to the movement through an all-anti G-quartet. Additionally, study of G-quadruplex structures formed by d(TG3T) and its modified analogs containing a 5’-5’ or 3’-3’ inversion of polarity sites revealed that the inter-quartet cavities at the inversion of polarity sites bind ammonium ions less tightly than a naturally occurring 5’-3’ backbone.
COBISS.SI-ID: 5132570
25 nt guanine rich vascular endothelial growth factor aptamer was studied with CD; UV and NMR spectroscopy. While unmodified aptamer folds into several G-quadruplex structures in the presence of potassium ions, modifications with locked and unlocked nucleotides lead to the stabilization of a single parallel structure with three G-quartets. Unusual features of the structure include five consecutive guanine residues that are all included in the G-quadruplex core, and a new type of D-shaped loop that brings isolated guanine residue in the G-quartet. The edgewise and propeller loops connect the remaining two G-rich tracts. 5' and 3' overhangs are well structured and were shown to importantly contribute to the formation of structurally pre-organized intermediates and stabilizations of the single G-quadruplex structure.
COBISS.SI-ID: 5373466
G-wires, continuous G-quadruplexes are a promising element for use in nanotechnology, particularly in molecular electronics. Previous investigation showed that some guanine-rich oligonucleotides with GC-termini can form long G-quadruplexes (G-wires), that are linked via G:C:G:C-quartets. To assess the role of GC-ends in G-wire formation in solution, we designed four analogous G-quadruple forming oligonucleotides, which differed in the number and position of GC-termini in the sequence. The core of oligonucleotide sequences was in all four cases the same d(GGTG4TGG) To compare their properties four different techniques were used: UV-spectroscopy, circular dichroism, NMR and dynamic light scattering. We concluded that formation of G:C:G:C-quartets is only possible at the 5'-terminus, while 3'-GC-termini cannot participate in G:C:G:C-quartets and therefore hinder the formation of longer structures. In the case when one of the G-quartets at the end of the quadruplex was not obstructed by a GC-terminus, stacking of G-quadruplexes was enabled. The longest G-quadruplex stacks were observed in the solution of oligonucleotide without GC-termini. Their estimated length was nearly 20 nm.
COBISS.SI-ID: 2606436