Biomedical subjects
Publications and source records attributed to A L Potyahaylo.
By UV spectroscopic data for anhydrous DMSO solutions and ab initio HF/6-31G** calculations in vacuum it was shown for the first time that deprotonated amino acid carboxylic group is able to change tautomeric state of a nucleotide base, exactly to convert the N9H ground-state prototropic tautomer of adenine into the N7H and N1H rare ones.
The 1H NMR and MNDO/H calculation data combined indicate the uracil and thymine tautomeric transitions from the ground diketo tautomeric state to the high-energy keto-enol one stimulated by specific interaction with carboxylate ion in anhydrous DMSO, which is blocked by base methylation at the 1 or 3 positions.
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.
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.
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.
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.
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.