39007-51-7Relevant academic research and scientific papers
Reaction of mucochloric and mucobromic acids with adenosine and cytidine: Formation of chloro- and bromopropenal derivatives
Kronberg, Leif,Asplund, Deanne,Maeki, Jukka,Sjoeholm, Rainer
, p. 1257 - 1263 (1996)
Mucochloric (MCA) and mucobromic acid (MBA)-bacterial mutagens and water disinfection byproducts-were reacted with adenosine, cytidine, and guanosine in N,N-dimethylformamide (DMF). In the MCA reaction with adenosine and cytidine and in the MBA reaction with adenosine one major product was formed. In the reactions of MBA with cytidine and in the reactions of MCA and MBA with guanosine only trace levels of products could be detected, and these were not further characterized. The products from the adenosine and cytidine reactions were isolated by preparative chromatography on octadecylsilane columns and structurally characterized by UV absorbance, 1H and 13C NMR spectroscopy, and mass spectrometry. The products were identified as 3-(N6- adenosinyl)-2-chloro-2-propenal (M(Cl)A), 3-(N6-adenosinyl)-2-bromo-2- propenal (M(Br)A), and 3-(N4-cytidinyl)-2-chloro-2-propenal (M(Cl)C). The yields of M(Cl)A, M(Br), A, and M(Cl)C were 19, 4, and 7 mol %, respectively. These halopropenal derivatives were formed also in reactions carried out in aqueous solutions at pH 7.4 and 37 °C at low yields, about 5 x 10-3%. The mechanism of formation of the halopropenal derivatives and of the previously identified etheno and ethenocarbaldehyde derivatives was elucidated by reacting 13C-3 labeled MCA with adenosine in DMF and in water. The location of the labeled carbon in the products was determined from the 13C NMR spectra. It was concluded that the halopropenal derivatives were formed by mechanisms that differ completely from the one responsible for the formation of the propenal adducts (M1A and M1C) previously reported to be formed in reactions of malonaldehyde with adenosine and cytidine.
A New One-Pot Fluorescence Derivatization Strategy for Highly Sensitive MicroRNA Analysis
Pan, Li,Zhang, Huaisheng,Zhao, Jingjin,Ogungbe, Ifedayo Victor,Zhao, Shulin,Liu, Yi-Ming
, p. 5639 - 5647 (2020/03/23)
MicroRNAs (miRNAs) modulate the expression of over 30 % of mammalian genes during development and apoptosis, and abnormal expression of miRNAs may lead to a range of human pathologies. Therefore, analysis of miRNAs is valuable for disease diagnostics. In this work, a novel one-pot fluorescence derivatization strategy was developed for miRNA analysis. The mechanism of the derivatization reaction was explored by using instrumental methods, including liquid chromatography, fluorescence spectroscopy, and mass spectrometry. Highly fluorescent N6-ethenoadenine (?-adenine) was formed and detached from the miRNA sequence through the reaction of adenine in nucleic acids with 2-chloroacetaldehyde (CAA) at 100 °C. This is the first experimental evidence that the cooperation of formed ?-adenine and water-mediated hydrogen-bond interaction between the proton at the 2′- and the oxyanion at 3′-positions stabilized the oxocarbenium significantly, which makes the depurination and derivatization of miRNA highly effective. Based on this derivatization strategy, a facile and sensitive high-performance liquid chromatography method was developed for quantitative assay of miRNAs. In combination with magnetic solid-phase extraction (MSPE), the HPLC method was shown to be useful for the determination of microRNAs at sub-picomolar level in serum samples.
The nucleoside transport proteins, NupC and NupG, from Escherichia coli: Specific structural motifs necessary for the binding of ligands
Patching, Simon G.,Baldwin, Stephen A.,Baldwin, Alexander D.,Young, James D.,Gallagher, Maurice P.,Henderson, Peter J. F.,Herbert, Richard B.
, p. 462 - 470 (2007/10/03)
A series of 46 natural nucleosides and analogues (mainly adenosine-based) were tested as inhibitors of [U-14C]uridine uptake by the concentrative, H+-linked nucleoside transport proteins NupC and NupG from Escherichia coli. The two evolutionarily unrelated transporters showed similar but distinct patterns of inhibition, revealing differing selectivities for the different nucleosides and their analogues. Binding of nucleosides to NupG required the presence of hydroxyl groups at each of the C-3′ and C-5′ positions of ribose, while binding to NupC required only the C-3′ hydroxyl substituent. The greater importance of the ribose moiety for binding to NupG is consistent with the evolutionary relationship between this protein and the oligosaccharide: H+ symporter (OHS) subfamily of the major facilitator superfamily (MFS) of transporters. For both proteins the natural α-configuration at C-3′ and the natural β-configuration at C-1′ was mandatory for ligand binding. N-7 in the imidazole ring of adenosine and the amino group at C-6 were found not to be important for binding and both transporters showed flexibility for substitution at C-6/N6; one or both of N-l and N-3 were important for adenosine analogue binding to NupC but significantly less so for binding to NupG. From the different effects of 8-bromoadenosine on the two transporters it appears that adenosine selectively binds to NupC in an anti- rather than a syn-conformation, whereas NupG is less prescriptive. The pattern of inhibition of NupC by differing nucleoside analogues confirmed the functional relationship of the bacterial transporter to members of the human concentrative nucleoside transporter (CNT) family and reaffirmed the use of the bacterial protein as an experimental model for these physiologically and clinically important mammalian proteins. The specificity data for NupG have been used to develop a homology model of the protein's binding site, based on the X-ray crystallographic structure of the disaccharide transporter LacY from E. coli. We have also developed an efficient general protocol for the synthesis of adenosine and three of its analogues, which is illustrated by the synthesis of [1′-13C]adenosine.
Reactions of adenosine with bromo- and chloromalonaldehydes in aqueous solution: Kinetics and mechanism
Mikkola, Satu,Koissi, Niangoran,Ketomaeki, Kaisa,Rauvala, Susanna,Neuvonen, Kari,Loennberg, Harri
, p. 2315 - 2323 (2007/10/03)
Reactions of adenosine nucleosides with halogen substituted acetaldehydes and malonaldehydes have been studied and pseudo first-order rate constants have been determined. All the reactions yield 1,N6-etheno adducts, and with malonaldehydes; in addition to this, 11-formyl-1,N6-etheno adducts are also formed. Particular attention has been paid to the formation of the formyletheno products. The results obtained suggest that the reactions of adenine base with halogenated acetaldehydes and malonaldehydes are basically similar. It also seems that in reactions of halomalonaldehydes with adenosine, the etheno and formyletheno products are formed through the same initial reaction pathway i.e. the attack of the 6-amino group of the adenine base at the carbonyl carbon atom of the aldehyde.
Formation of etheno adducts of adenosine and cytidine from 1-halooxiranes. Evidence for a mechanism involving initial reaction with the endocyclic nitrogen atoms
Guengerich, F. Peter,Raney, Veronica M.
, p. 1074 - 1080 (2007/10/02)
The etheno derivatives of nucleic acid bases contain an additional ring and are of interest because of their useful fluorescence properties and their potential as mutagenic lesions in DNA. The mechanism of formation from 2-haloacetaldehydes is known to involve initial Schiff base formation at an exocyclic nitrogen; however, mechanisms of formation from the more relevant 1-substituted oxiranes have not been established. The reaction of N6-methyladenosine (5) with 1-chlorooxirane yielded the stable carbinolamine 7,8-dihydro-8-hydroxy-9-methyl-3-β-D-ribofuranosylimidazo[2,1-i]purinium species (10), consistent with initial attack of the N1 atom of adenine at the methylene of 1-chlorooxirane. No products indicative of initial reaction at the N6 atom of adenine were found. Reaction of 2,2-dibromoethanol with adenosine or cytidine at pH 9.2 yielded 1,N6-ethenoadenosine (1) or 3,N4-ethenocytidine (2), respectively, presumably via the base-catalyzed formation of 1-bromooxirane from the bromohydrin. When reactions were done with 2,2-dibromo[1-13C]ethanol, 1 contained label only at C-7 and 2 contained label only at C-3. A role for 2-bromoacetaldehyde in these reactions was ruled out by the lack of incorporation of deuterium from 2H2O into 1 under conditions where the exchange of the methylene protons of 2-bromoacetaldehyde with the solvent was relatively rapid. The collective results are most consistent with a mechanism in which the basic endocyclic nitrogen (N1 of adenine or N3 of cytosine) reacts with the methylene carbon of the 1-halooxirane, and, after ring opening and loss of the leaving group, the resulting aldehyde reacts with the exocyclic nitrogen to form the additional ring.
Structural Alteration of Nucleic Acid Bases by Bromomalonaldehyde
Nair, Vasu,Offerman, Rick J.,Turner, Gregory A.
, p. 4021 - 4025 (2007/10/02)
Bromomalonaldehyde (BMDA), prepared by bromination of malonaldehyde with elemental bromine, has been employed to modify a number of nucleic acid bases.These reactions transform pyrimidine and purine bases into modified systems containing etheno and etheno carboxaldehyde moieties, among other products.The structures of these modified bases were established by UV, mass spectral, and high-field NMR data.Fluorescence emission data for some of the adducts are of significance.The general mechanism of modification is discussed.
COMPARATIVE STUDIES ON REACTIONS OF ADENOSINE AND CYTIDINE WITH CHLOROACETALDEHYDE, Α-BROMOPROPIONALDEHYDE AND CHLOROACETONE. SYNTHESIS OF 1,N6-ETHENOADENOSINE AND 3,N4-ETHENOCYTIDINE DERIVATIVES METHYLATED AT THE ETHENO BRIDGE
Krzyzosiak, Wlodzimierz J.,Biernat, Jacek,Ciesiolka, Jerzy,Gornicki, Piotr,Wiewiorowski, Maciej
, p. 779 - 787 (2007/10/02)
The rates of individual steps of the reactions of adenosine and cytidine with chloroacetaldehyde, α-bromopropionaldehyde and chloroacetone in water were compared.It was found that the nucleosides reacted with both α-haloaldehydes at comparable rates.The first reaction step, i.e. formation of the cyclic carbinolamine intermediate was ca. twice faster in the α-bromopropionaldehyde reactions, whereas the second, i.e. dehydration, was 1.5 time more rapid in the case of chloroacetaldehyde.In the chloroacetone reactions the rate-determining step was the slow initial addition and no intermediates were observed.The final products of α-bromopropionaldehyde and chloroacetone reactions were characterized by FD-MS, UV and 1H NMR methods.
Intramolecular Association of 1,N6-Ethenoadenylyl-(3'-->5')-1,N6-ethenoadenosine (εApεA). A Comparison of Intramolecular Stacking Equilibrium Quotients Estimated by Different Methods
Inoue, Yasuo,Kuramochi, Takao,Sakurai, Michiharu,Tazawa, Ichiro
, p. 5574 - 5577 (2007/10/02)
Two approaches were taken to determine the intramolecular stacking equilibrium quotients in aqueous solution at 25 deg C for 1,N6-ethenoadenylyl-(3'-->5')-1,N6-ethenoadenosine (εApεA), one involving measurements of the temperature dependence of the ultraviolet absorption spectrum and the other, measurements of the ionization constants of εApεA and the component monomers.The values estimated by these two alternative methods are in agreement with the previous finding based on fluorescence techniques, strongly indicating the validity of the so-called "two-state model" for the intramolecular stacking equilibrium system of εApεA.These values of the equilibrium quotient for the intramolecular stacking association of εApεA are also compared with that for the corresponding intermolecular association.
