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
S100A1 is a member of the Ca2+ binding S100 protein family. It is expressed in brain and heart tissue, where it plays a crucial role as a modulator of Ca2+ homeostasis, energy metabolism, neurotransmitter release, and contractile performance. Biological effects of S100A1 have been attributed to its direct interaction with a variety of target proteins. The (patho)physiological relevance of S100A1 makes it an important molecular target for future therapeutic intervention. S-Nitrosylation is a post-translational modification of proteins, which plays a role in cellular signal transduction under physiological and pathological conditions. We described high resolution 3D structures of human apo-S100A1 protein with the Cys85 thiol group in reduced and S-nitrosylated states. Although the typical S100 protein inter subunit four-helix bundle is conserved upon S-nitrosylation, the conformation of S100A1 protein is reorganized at the sites most important for target recognition (i.e. the C-terminal helix and the linker connecting two EF-hand domains).
COBISS.SI-ID: 5132826
In this work, we described a general route toward congested o-(branched alkoxy)-tertbutoxybenzenes starting from the corresponding catechols and their application to the synthesis of congested phosphorus-based compounds. In particular, to date no reliable access was available to such compounds. The preparation reported by Horner and Simons of di-tertbutoxybenzene and its phosphine derivative proved to be wrong as it turned out that their procedure does not allow preparation of such compounds. Within this work we succedded to develop a reliable route to the desired ortho-di-tert-butoxybenzene and its derivatives. Also we carried out a lengthy study for O,O’-di-tert-butylation of various catechols. These new bulky arenes are highly sought especially in ligand synthesis and constitute crucial starting materials for the synthesis of metal catalysts.
COBISS.SI-ID: 5119258