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D M Hovorun

Publications and source records attributed to D M Hovorun.

13 recordsLinked to original sources
PubMed2005

To what extent can methyl derivatives be regarded as stabilized tautomers of xanthine?

Taking xanthine (Xan) as an example, validity of an approach to experimental investigations of nucleotide bases' tautomeric equilibrium, based on the use of methyl derivatives corresponding to their prototropic tautomers, was studied by (1)H NMR in dimethylsulfoxide (DMSO) and by quantum chemical calculations at the B3LYP/6-311++G(d,p) level of theory. From (1)H NMR spectra of m(7)Xan, m(9)Xan, Xan and m(3)Xan conclusion was made that the N7H tautomeric forms of the last two compounds dominate in solution, which was supported by quantum chemical data. Calculated relative energies of the N9H tautomers of Xan and m(3)Xan (8.74 and 9.57 kcal/mol, accordingly) are rather close to the m(9)Xan one (9.11 kcal/mol). Nonspecific influence of DMSO modelled by the COSMO algorithm therewith reduces these values by approximately 2-3 kcal/mol. The data obtained imply that methyl derivatives are rather good models of high-energy tautomers of nucleotide bases, if their relative energies are not less than a few kcal/mol.

Calorimetry↗
PubMedDate not supplied

Structural transitions in polyadenylic acid and hypothesis on biological role of its double-stranded forms.

Under various conditions poly(A) exists in different forms such as single-stranded helix, two double-helical forms and others. The formation of double-stranded helices is induced by adenine protonation. Under physiological ionic strengths they are formed at acidic pH, but under the same conditions methylated poly(A) has double-stranded structure at alkaline pH. Since the shift of adenine protonation pKa to alkaline region may be caused not only by chemical modification of poly(A) but also its interaction with proteins, it is quite probable that double oligo(A)-helices are formed in the living cell as well. In this article the hypothesis on possible biological role of poly(A) double-stranded forms has been discussed in details. The models of involvement of double oligo(A)-sequences of RNA in such intracellular processes as termination of mRNA poly(A) tails synthesis and autoregulation of poly(A)-binding protein synthesis are suggested as an example.

Nucleic Acid Conformation↗
PubMedDate not supplied

The prototropic tautomerism of nitrogen bases: a new insight into the old problem.

The summary is made of the series of theoretical calculations performed by the semiempirical quantum-chemical AM1 method of physico-chemical features of prototropic tautomerism of nucleotide bases with full optimization of all parameters. Applying of nontraditional approach based on the view that the highest possible number of prototropic tautomers of bases are determined by an overall quantity of protons and electron lone pairs of proton acceptor atoms, the success was achieved in ascertaining that, as regards prototropic tautomerism, nucleotide bases are more mobile structures (prototropic tautomerism of nucleotide bases has a molecular-zwitterionic character involving carboprotons as well) than it was assumed earlier. A biological significance of the data obtained, which are generalized and may be extended from the authors point of view to more wide range of objects, amino acids included.

Molecular Structure↗
PubMedDate not supplied

[Specific interactions of isoguanine with the neutral and deprotonated carboxylic group of amino acids: results of model quantum chemical calculations].

The MNDO/H quantum chemical calculations performed in order to estimate energetic features of the isoguanine (isoGua) prototropic tautomers complexes with acetic acid and its carboxylate-ion (models of neutral and deprotonated forms of amino acid carboxylic group) demonstrate ability of the latter to induce the N9H-->N7H tautomeric transition in the base, being characteristic to other purine bases as well. By contrast, the neutral carboxylic group forms the most stable complex with the ground-state isoGua tautomer N3HN9H.

Amino Acids↗
PubMedDate not supplied

UV spectra of guanine methyl and glycosyl derivatives and their transformations induced by interactions with amino acids via carboxylic group in dimethylsulfoxide.

UV absorption spectra of guanine derivatives m9Gua, m(2)2,9Gua, m1Gua, m(2)1,7Gua, m3Gua, G, dG, m1G, m2G, m7G, as well as guanine analogue isoGua were studied in anhydrous dimethylsulfoxide (DMSO). Changes in UV absorption spectra of guanine derivatives in the presence of amino acid derivatives with neutral carboxylic group (ac-Asp, ac-Glu, ac-Gly, ac-Asp-OMe) or deprotonated carboxylic group (NaAc, f-Gly-ONa) were investigated and interpreted. The m1Gua and m7Gua derivatives were shown to exist as the N9H tautomers in anhydrous DMSO. The majority of examined guanine derivatives were determined to interact with deprotonated carboxylic group only, except of m7G, isoGua and m3Gua, which are able to form complexes with neutral carboxylic group as well.

Amino Acids↗
PubMedDate not supplied

Recognition modes of hypoxanthine, xanthine and their derivatives by amino acid carboxylic group: UV spectroscopic and quantum chemical data.

UV absorption spectra of Hyp, Xan, their nucleosides and methyl derivatives were studied in anhydrous dimethylsuloxide and the changes in these spectra on the interactions with neutral and deprotonated carboxylic groups of amino acids were traced. By the semiempirical quantum-chemical method MNDO/H it was shown, that interaction with carboxylate-ion fixes Hyp as the rare N7H enolic tautomer and converts Xan into its N9H diketo tautomeric form with a probable admixture of the N7H O6-enolic form. Significant changes in the UV spectra of Xan, m3Xan, m9Xan and X under interaction with carboxylate-ion are determined by essential contribution to complex formation of proton transfer from bases to ligands, m9Xan and X proving to be slightly protonated even by the solvent. The methylation of the N7 position in m7I and m7X was established to result in the practical absence of their interactions with carboxylate-ion and initiation of a new ability of forming complex with the neutral carboxylic group. Substitution of the C8H group by N in 8-azaXan does not change the interaction specificity of the base with two forms of carboxylic group.

Amino Acids↗
PubMedDate not supplied

[UV spectra of adenine methyl and glycosyl derivatives and their transformation induced by amino acid carboxylic groups].

UV absorption spectra of adenine, adenosine and their methyl derivatives were studied in dimethylsuloxide (DMSO). Considerable changes in UV spectra of adenine under methylation at the 1 and 3 positions, and adenosine under methylation at the 1 position attested the essential structural reconstruction of adenine purine ring. Ade and m6Ade were shown to form complexes with deprotonated carboxylic group of amino acids (carboxylate-ion) through two H-bonds involving amino group and N7H imino group, tautomeric transition N9H-->N7H being initiated namely by interaction with carboxylate-ion. Considerable changes in UV spectra of m1Ade, m1A, and m3Ade under interaction with neutral carboxylic group of amino acids were interpreted as a result of proton transfer from amino acid to the base.

Adenine↗
PubMedDate not supplied

Specific interaction of isocytosine and amino acid carboxylic group shifts the base tautomeric equilibrium.

By 1H NMR, UV and IR spectroscopies in anhydrous DMSO and quantum-chemical calculations by MNDO/H in vacuum specific interactions of isocytosine with neutral and deprotonated carboxylic groups of amino acids were investigated. In vacuum interaction with carboxylate ion provokes in isoCyt transition from the ground-state enolic form to the high energy N3H-keto tautomer. In DMSO keto tautomer N3H of isoCyt is stabilized but interactions with carboxylate ion essentially shifts equilibrium to enolic form. Neutral carboxylic group forms the most stable complex with the ground-state enolic tautomer in vacuum but in DMSO it proves to shift the keto(N3H)-enolic equilibrium to the right.

Amino Acids↗
PubMedDate not supplied

[Effect of carboxylate and Na ions on the tautomeric status of 9-methylguanine].

Interactions of 9-methylguanine (m9Gua) with carboxylate ion of acetic acid (CH3COO-) and Na+ were studied by 1H NMR spectroscopy and ab initio quantum chemical calculations of the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels of theory. Changes in the m9Gua 1H NMR spectrum in the presence of the equimolar amount of sodium acetate (NaAc), which in anhydrous DMSO dissociates to CH3COO- and Na+, were interpreted as a consequence of a complex formation of m9Gua in the amino-keto-N1H tautomeric form (m9GuaN1H) with carboxylate ions via two H-bonds involving amino and N1H-imino protons. Quantum chemical calculations of interactions of the m9GuaN1H ground-state tautomer and the m9GuaN3H high energy one with relative energy 20.01 kcal/mol show that the ground state tautomer forms the ground-state complex CH3COO-:mgGuaN1H, by 5.57 kcal/mol more stable than the CH3COO-:m9GuaN3H complex, and coordination of Na+ with the O6 and N7 atoms reduces this energy difference to 2.57 kcal/mol. Such a coordination of Na+ with tautomer m9GuaN3H therewith decreases its relative energy only to 13.31 kcal/mol. Non-additivity of the two ligands contributions to the 8-times reduction of the relative energy of the high energy tautomer in the CH3COO-:m9GuaN3H:Na+(O6,N7) triple complex was concluded, the role of CH3COO- being dominant. Besides, coordination with Na+ resulted in an iminoproton transfer from the base to CH3COO- in the triple complexes of both tautomers, according to calculations in vacuum. Biological significance of the results is noticed.

Guanine↗
PubMedDate not supplied

Dimer linkage structure in retroviruses: models that include both duplex and quadruplex domains.

Genome of all known retroviruses consists of two identical molecules of RNA, which are non-covalently linked. The most stable contact site between two RNA molecules is located near their 5' ends. The molecular interactions in the dimer linkage structure (DLS) in mature virions are currently unknown. Recently we suggested that the dimer linkage structure in human immunodeficiency virus 1 (HIV-1) contains both duplex and quadruplex domains and proposed a model of DLS in HIV-1Mal (Central African virus). In this paper we showed that similar models can be also built for HIV- 1Lai, a representative of the North-American and European viruses. One of the double-stranded domains in the model structures represents either an extended duplex formed by different pathways (through base pair melting and subsequent reannealing or by a recombination mechanism) or kissing loop complex. The quadruplexes contain both G- and mixed tetrads, for example, G.C.G.C or A.U.A.U. Phylogenetic analysis of 350 isolates from NCBI database showed that similar models of DLS are predictable practically for all HIV-1 isolates surveyed. A model of dimer linkage structure in Moloney murine sarcoma virus (MuSV) is also presented. The structure includes a duplex formed by the palindromic sequences and several quadruplexes.

Animals↗