RESUMO
A series of tripeptides TrpTrpPhe (1), TrpTrpTyr (2), and TrpTrpTyr[CH2N(CH3)2] (3) were synthesized, and their photophysical properties and non-covalent binding to polynucleotides were investigated. Fluorescent Trp residues (quantum yield in aqueous solvent ΦF = 0.03-0.06), allowed for the fluorometric study of non-covalent binding to DNA and RNA. Moreover, high and similar affinities of 2×HCl and 3×HCl to all studied double stranded (ds)-polynucleotides were found (logKa = 6.0-6.8). However, the fluorescence spectral responses were strongly dependent on base pair composition: the GC-containing polynucleotides efficiently quenched Trp emission, at variance to AT- or AU-polynucleotides, which induced bisignate response. Namely, addition of AT(U) polynucleotides at excess over studied peptide induced the quenching (attributed to aggregation in the grooves of polynucleotides), whereas at excess of DNA/RNA over peptide the fluorescence increase of Trp was observed. The thermal denaturation and circular dichroism (CD) experiments supported peptides binding within the grooves of polynucleotides. The photogenerated quinone methide (QM) reacts with nucleophiles giving adducts, as demonstrated by the photomethanolysis (quantum yield ΦR = 0.11-0.13). Furthermore, we have demonstrated photoalkylation of AT oligonucleotides by QM, at variance to previous reports describing the highest reactivity of QMs with the GC reach regions of polynucleotides. Our investigations show a proof of principle that QM precursor can be imbedded into a peptide and used as a photochemical switch to enable alkylation of polynucleotides, enabling further applications in chemistry and biology.
Assuntos
Indolquinonas/química , Oligopeptídeos/química , Processos Fotoquímicos , Poli A-U/química , Desaminação , Triptofano/químicaRESUMO
We have reported the interaction of two flavonoids namely quercetin (Q) and morin (M) with double stranded poly(A).poly(U) (herein after A.U) and triple stranded poly(U).poly(A)*poly(U) (herein after U.A*U, dot represents the Watson-Crick and asterisk represents Hoogsteen base pairing respectively) in this article. It has been observed that relative positions of hydroxyl groups on the B-ring of the flavonoids affect the stabilization of RNA. The double strand as well as the triple strand of RNA-polymers become more stabilized in presence of Q, however both the duplex and triplex remain unaffected in presence of M. The presence of catechol moiety on the B-ring of Q is supposed to be responsible for the stabilization. Moreover, after exploiting a series of biophysical experiments, it has been found that, triple helical RNA becomes more stabilized over its parent duplex in presence of Q. Fluorescence quenching, viscosity measurement and helix melting results establish the fact that Q binds with both forms of RNA through the mode of intercalation while M does not bind at all to either forms of RNA.
Assuntos
Flavonoides/química , Poli A-U/química , Poli U/química , Pareamento de Bases , Sítios de Ligação , Fenômenos Biofísicos , Estabilidade de Medicamentos , Polarização de Fluorescência , Ligação de Hidrogênio , Hidroxilação , Estrutura Molecular , Conformação de Ácido Nucleico , Quercetina/química , Espectrometria de Fluorescência , EspectrofotometriaRESUMO
To reveal the effect of DNA- or RNA-specific low-molecular compounds on cellular processes on the molecular level, we have carried out the studies with the application of spectroscopic methods. It is necessary for the understanding of structural-functional properties of nucleic acids in cell. In this work the interaction of DNA-specific thiazine dye methylene blue (MB) with synthetic polynucleotides poly(rA) and poly(rU) was studied. The interaction of MB with synthetic polyribonucleotides poly(rA) and poly(rU) was examined in the solution with high ionic strength in a wide phosphate-to-dye (P/D) range, using the absorption and fluorescence spectroscopies, as well as the fluorescence 2D spectra and 3D spectra analyses were given. Values of the fluorescence quenching constants for the complexes of MB with poly(rA) and poly(rU) were calculated (KSV is the Stern-Volmer quenching constant). Two different modes of MB binding to single-stranded (ss-) poly(rA) and poly(rU) and to their hybrid double-stranded (ds-) structure - poly(rA)-poly(rU) were identified. This ligand binds to ss-poly(rA) and poly(rA)-poly(rU) by semi-intercalation and electrostatic modes, but to ss-poly(rU) the prevailing mode is the electrostatic interaction.Communicated by Ramaswamy H. Sarma.
Assuntos
Azul de Metileno , Poli A-U , Azul de Metileno/química , Poli A-U/química , Conformação de Ácido Nucleico , Poli A/química , DNA/químicaRESUMO
The interaction of coralyne with poly(A)*poly(U), poly(A)*2poly(U), poly(A) and poly(A)*poly(A) is analysed using spectrophotometric, spectrofluorometric, circular dichroism (CD), viscometric, stopped-flow and temperature-jump techniques. It is shown for the first time that coralyne induces disproportionation of poly(A)*poly(U) to triplex poly(A)*2poly(U) and single-stranded poly(A) under suitable values of the [dye]/[polymer] ratio (C(D)/C(P)). Kinetic, CD and spectrofluorometric experiments reveal that this process requires that coralyne (D) binds to duplex. The resulting complex (AUD) reacts with free duplex giving triplex (UAUD) and free poly(A); moreover, ligand exchange between duplex and triplex occurs. A reaction mechanism is proposed and the reaction parameters are evaluated. For C(D)/C(P)> 0.8 poly(A)*poly(U) does not disproportionate at 25 degrees C and dye intercalation into AU to give AUD is the only observed process. Melting experiments as well show that coralyne induces the duplex disproportionation. Effects of temperature, ionic strength and ethanol content are investigated. One concludes that triplex formation requires coralyne be only partially intercalated into AUD. Under suitable concentration conditions, this feature favours the interaction of free AU with AUD to give the AUDAU intermediate which evolves into triplex UAUD and single-stranded poly(A). Duplex poly(A)*poly(A) undergoes aggregation as well, but only at much higher polymer concentrations compared to poly(A)*poly(U).
Assuntos
Antibacterianos/química , Alcaloides de Berberina/química , Poli A-U/química , Dicroísmo Circular , Etanol/química , Cinética , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Poli A/química , Cloreto de Sódio/química , Espectrometria de Fluorescência , Análise Espectral , Termodinâmica , ViscosidadeRESUMO
BACKGROUND: The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors. RESULTS: Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA. CONCLUSIONS: Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.
Assuntos
Proteínas Arqueais/metabolismo , Exorribonucleases/metabolismo , Proteínas Arqueais/química , Exorribonucleases/química , Poli A/química , Poli A/metabolismo , Poli A-U/química , Poli A-U/metabolismo , Ligação Proteica , Pyrococcus abyssi/metabolismo , Estabilidade de RNA , RNA Arqueal/metabolismoRESUMO
On the basis of molecular biophysics, a methodology for the analysis of intramolecular structural order of the polynucleotide duplex poly(A).poly(U) has been developed. It was shown that the combination of circular dichroism spectroscopy with differential scanning calorimetry is an optimal approach, which ensures the screening of a wide set of substances and interaction conditions and the choice of compound(s) that can stabilize the structure and increase the biological activity of this duplex. The study is aimed at obtaining a new and highly active antiviral remedy.
Assuntos
Antivirais/química , Compostos de Platina/química , Poli A-U/química , Dicroísmo Circular/métodosRESUMO
Two new Ru(II) polypyridyl complexes containing fluorine substituents, [Ru(bpy)2(o-fpip)]2+ (Ru1, bpy=2,2'-bipyridine, o-fpip=2-(2-fluorophenyl)imidazo[4,5-f] [1,10]phenanthroline) and [Ru(bpy)2(p-fpip)]2+ (Ru2, p-fpip=2-(4-fluorophenyl)imidazo[4,5-f] [1,10]phenanthroline) have been synthesized as binders for poly(U)â¢poly(A)∗poly(U) triplex RNA. The binding of the two complexes with the triplex RNA has been investigated by spectroscopic methods and viscosity measurements. Analysis of the electronic absorption spectra indicates that the association of intercalating Ru2 with the triplex RNA is greater than that of Ru1, which is also supported by spectroscopic titrations and viscosity measurements. Thermal denaturation studies reflect that third-strand stabilization depend on the nature of the two complexes and Ru2 is more effective for stabilization of the triplex RNA. Circular dichroism spectra of the triplex RNA in the presence of metal complexes indicate that the binding-induced CD perturbation of the triplex structure is more obvious by Ru2. The main results obtained here suggest that the positions of fluorine substituent in the intercalating ligands have a significant effect on the two complexes stabilizing the third strand.
Assuntos
Complexos de Coordenação/química , Hidrocarbonetos Fluorados/química , Substâncias Intercalantes , Poli A-U/química , Poli U/química , Rutênio/química , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/químicaRESUMO
We employed UV light absorption and circular dichroism (CD) spectroscopic measurements to study the binding of novel water-soluble porphyrins meso-tetra-(4N-allylpyridyl)porphyrin [TAlPyP4], and its Ag containing derivative to the poly(rA)poly(rU) and poly(rI)poly(rC) RNA duplexes. Our results suggest that TAlPyP4 associate with the duplexes via intercalation, whereas the conservative CD spectra indicates that AgTAlPyP4 preferably binds via outside self-stacking mode. We used our determined binding isotherms for each ligand-RNA binding event to calculate the binding constant, Kb, and binding free energy, DeltaGb = -RTlnKb. By performing these experiments as a function of temperature, we evaluated the van't Hoff binding enthalpies, DeltaH. The binding entropies, DeltaSb, were calculated as DeltaSb = (DeltaHb - DeltaGb)/T. We interpret our data in terms of specific interactions that stabilize/destabilize each ligand-RNA complex studied in this work. Taken together, our data provide important new information about the thermodynamics of interactions of porphyrins with nucleic acids.
Assuntos
Poli A-U/metabolismo , Poli I-C/metabolismo , Porfirinas/metabolismo , Termodinâmica , Poli A-U/química , Poli I-C/química , Porfirinas/químicaRESUMO
This communication presents synthesis and spectral characterization of metalloporphyrin [Zn(X)TMPyP4] (TMPyP4 is 5,10,15,20-tetrakis (N-methylpyridinium-4-yl)porphyrin), and studies its binding onto anionic surface sites of synthetic double stranded polynucleotide Poly(A)-Poly(U). [Zn(X)TMPyP4] binding with Poly(A)-Poly(U) was monitored by UV-Vis absorbance spectroscopy, two fluorescence spectroscopies and 1H NMR in a working aqueous medium of 0.15M ionic strength, pH7.0 and at 25°C. The evidence provided by spectroscopic measurements and multivariate data analysis suggests the use of this metalloporphyrin as a probe for investigation of the polynucleotide surface. In contrast to TMPyP4 intercalation, an outside adsorption of [Zn(X)TMPyP4] induces an attenuation of luminescence intensity and has little influence on the shape of luminescence band. Special attention was paid to the quantitative description of the interaction between neighboring ligands on the Poly(A)-Poly(U) surface. The intrinsic binding constant to an isolated binding site lgKin 5.8±0.1, the cooperativity parameter ω 1.8±0.2, and number of monomers occupied by a ligand n=2 (25°C; pH7.0) were calculated based upon the recently proposed non-linear least-squares fitting procedure. The discovered cooperativity of binding of [Zn(X)TMPyP4] metalloporphyrin to Poly(A)-Poly(U) is significantly lower as compared to free porphyrin TMPyP4, reflecting minimal mutual influence between the nearest neighboring ligands bound with functional PO4(-) groups of the polynucleotide surface.
Assuntos
Metaloporfirinas/química , Poli A-U/química , RNA de Cadeia Dupla/químicaRESUMO
In this work, we investigate the compaction activity of a sequential alpha,epsilon-peptide composed of l-lysines towards two RNA targets, in view of its possible pharmaceutical application in RNA-targeting and RNA delivery. The basic oligolysine, object of the present study, proved not only to be efficient in compacting the single-stranded polyA RNA, but also to strongly interact with the polyA·polyU complex, as evidenced by CD-binding and UV-melting experiments. In particular, the marked differences in the CD spectra of the RNA targets upon addition of the peptide, as well as the different UV melting behaviour for the polyA·polyU complex in the presence and absence of the peptide, sustain the hypothesis of a strong RNA compaction capacity of the alpha,epsilon-oligolysine. Finally, by using HPLC analysis, we found a good resistance of the peptide against the lytic action of human serum, an important requirement in view of in vitro/in vivo biological assays.
Assuntos
Poli A-U/química , Polilisina/química , RNA/química , Cátions , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Humanos , Conformação de Ácido Nucleico , Conformação Proteica , Estabilidade de RNA , Soro/química , Espectrofotometria Ultravioleta , TemperaturaRESUMO
Powders and films of variably hydrated poly(U), poly(A) and poly(A):poly(U) were X-irradiated at 4 K. Spectra and free radical yields were acquired at 4 K using Q-band EPR spectroscopy. Evidence for electron transfer from the hydration layer to the RNA bases, supporting in part the damage transfer hypothesis of Gregoli et al. (Radiat. Res. 89, 238-254, 1985), is presented. Based on measurements of radical yield as a function of hydration, we propose that intermolecular packing and polymer conformation are dominant factors in determining free radical trapping ability in these polymers. Our annealing results indicate that increasing hydration facilitates intercluster combination reactions.
Assuntos
Conformação de Ácido Nucleico/efeitos da radiação , Poli A-U/efeitos da radiação , Poli A/efeitos da radiação , Poli U/efeitos da radiação , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Análise dos Mínimos Quadrados , Poli A/química , Poli A-U/química , Poli U/química , Relação Estrutura-Atividade , Termodinâmica , Raios XRESUMO
Shape and dimension of the preferred nucleotide repeats in nucleic acids are found to depend on whether the sugar-phosphate linkage is of 2',5' or 3',5' type. It is shown that a nucleotide which is "compact" in 3',5' nucleic acids is rendered "extended" and vice versa for a given sugar pucker. It is interesting that this feature is accompanied by a switch in the preferred sugar ring conformation in 3',5' and 2',5' nucleic acids. 3' ribose and 3' deoxyribose rings (in 2',5' linkages) tend to favour C2' endo and C3' endo puckers respectively in contrast to C3' endo and C2' endo puckers favored by 2' ribose and 2' deoxyribose sugars (in 3',5' linkages). The distinguishable features between the nucleotide repeats of 3',5' and 2',5' nucleic acids need to be recognised while discussing their structural properties, as well as those of a variety of complexes that could be formed involving 2',5' and 3',5' strands of DNA and RNA. Ability and stability, or lack of them, for formation of a specific combination of these complexes may be directly related to the stereochemical constraints imposed as a consequence of conformationally homogeneous or heterogeneous nature of the repeating nucleotides of the complexing chains. As a first step towards delineating stereochemical features that distinguish 2',5' nucleic acids from their naturally occurring isomer A and B type helices have been modelled using the new concept of "compact" and "extended" nucleotide repeat that seemingly unifies helix generation of both types of linkages. Helical models for 2',5' RNA with "dinucleotide" repeat based on the crystal structure of 2',5' ApU have also been obtained.
Assuntos
Conformação de Ácido Nucleico , Ácidos Nucleicos/química , Carboidratos , Cristalografia por Raios X , Modelos Moleculares , Poli A-U/química , SoluçõesRESUMO
Phase transitions were studied of the sodium salt of poly(rA).poly(rU) induced by elevated temperature without Ni(2+) and with Ni(2+) in 0.07 M concentration in D(2)O (approximately 0.4 [Ni]/[P]). The temperature was varied from 20 degrees C to 90 degrees C. The double-stranded conformation of poly(rA).poly(rU) was observed at room temperature (20 degrees C-23 degrees C) with and without Ni(2+) ions. In the absence of Ni(2+) ions, partial double- to triple-strand transition of poly(rA).poly(rU) occurred at 58 degrees C, whereas only single- stranded molecules existed at 70 degrees C. While poly(rU) did not display significant helical structure, poly(rA) still maintained some helicity at this temperature. Ni(2+) ions significantly stabilized the triple-helical structure. The temperature range of the stable triple-helix was between 45 degrees C and 70 degrees C with maximum stability around 53 degrees C. Triple- to single-stranded transition of poly(rA).poly(rU) occurred around 72 degrees C with loss of base stacking in single-stranded molecules. Stacked or aggregated structures of poly(rA) formed around 86 degrees C. Hysteresis took place in the presence of Ni(2+) during the reverse transition from the triple-stranded to the double-stranded form upon cooling. Reverse Hoogsteen type of hydrogen-bonding of the third strand in the triplex was suggested to be the most probable model for the triple-helical structure. VCD spectroscopy demonstrated significant advantages over infrared absorption or the related electronic CD spectroscopy.
Assuntos
Níquel/química , Poli A-U/química , Poli A/química , Poli U/química , Fenômenos Biofísicos , Biofísica , Dicroísmo Circular , Íons , Modelos Químicos , Conformação de Ácido Nucleico , Sais/química , Espectrofotometria Infravermelho/métodos , TemperaturaRESUMO
The interaction of antimalarial drug quinacrine (QA) with polynucleotides is studied by UV-visible absorption, fluorescence and surface-enhanced Raman spectroscopy (SERS). The polynucleotides employed for such a study were calf thymus DNA, poly(A).poly(T), poly(A).poly(U), poly(C).poly(G) and poly(dG-dC).poly(dG-dC). Absorption and fluorescence spectra of QA complexes indicate that an interaction with the biomolecule is taking place, although different interaction mechanisms are probable depending on the sequence. The SERS spectra also reflect spectral changes which depend on the polymer sequence and that can be correlated to those observed by fluorescence, with the advantage of the detailed structural information provided by this vibrational technique. QA interacts with polynucleotides through its diprotonated form and by ring stacking. The strength of such interaction is extremely sequence dependent, thus suggesting different interaction mechanisms in each case. The SERS technique allows the simultaneous study of those polynucleotide moieties that are directly involved in the interaction thanks to the short-range character of the SERS spectroscopy. The interaction of QA with the above nucleic acids lead to a different change in the chain stability and flexibility which is further related to the different denaturation tendency of the polymer in the presence of the metal surface.
Assuntos
Antimaláricos/farmacologia , Ácidos Nucleicos/química , Ácidos Nucleicos/efeitos dos fármacos , Quinacrina/farmacologia , Animais , Antimaláricos/química , Sequência de Bases , Bovinos , DNA/química , DNA/efeitos dos fármacos , Técnicas In Vitro , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Substâncias Macromoleculares , Ácidos Nucleicos/genética , Poli A/química , Poli A-U/química , Poli C/química , Poli G/química , Poli T/química , Polidesoxirribonucleotídeos/química , Quinacrina/química , Espectrometria de Fluorescência , Espectrofotometria , Espectrofotometria Ultravioleta , Análise Espectral RamanRESUMO
Diffraction patterns from oriented polycrystalline specimens of fibrous polymers sometimes contain features indicating that the constituent microcrystallites are disordered. Such disorder affects the relationship between the crystal structure and the diffracted intensities. Therefore, the effects of disorder must be considered when determining structures from fibre diffraction data. Theory is developed here that describes the intensities diffracted by disordered polycrystalline fibres, and is used to calculate diffraction patterns from stimulated specimens with various kinds of disorder. The results show how Bragg and continuous diffraction are distributed on such diffraction patterns, and implications for structure determination are discussed.
Assuntos
Modelos Teóricos , Estrutura Molecular , Difração de Raios X , Cristalização , Poli A-U/química , Polidesoxirribonucleotídeos/químicaRESUMO
This paper reports evidence obtained by circular dichroism (CD) spectroscopy measurements indicating that two oligoribonucleotide duplexes with the alternating purine-pyrimidine sequences r(GC)6 or r(AU)6 change their A-RNA conformation under high pressure. Under the high-pressure conditions at which B-Z-DNA transition easily occurs, RNA acquires a conformation which only differs slightly from that of A-RNA. However, exposure of r(GC)6 or r(AU)6 to high pressure (6 kbar) in the presence of 5 M NaCl causes a conformation change of both oligoribonucleotide duplexes from their A- to their Z-RNA form. The departure of RNA or DNA duplexes from their original conformations under high pressure depends on the water structure itself and involves displacing an active (structural) water molecule outside the nucleic acid molecules. Experiments carried out until now in many laboratories have shown that B-Z or A-Z transitions of DNA or RNA, respectively, do not depend on the conditions applied, but the common mechanism for these processes seems to be dehydration. This same effect can be observed either at high salt concentrations or in the presence of an alcohol or at high pressure. Our results also support the view that the higher stability of RNA compared with DNA duplexes is due to the strong interaction of the 2'-hydroxyl groups of RNA with water molecules.
Assuntos
Conformação de Ácido Nucleico , Poli A-U/química , Poli C/química , Poli G/química , Pressão , RNA/química , Dicroísmo Circular , Cloreto de Magnésio/farmacologia , Conformação de Ácido Nucleico/efeitos dos fármacos , Concentração Osmolar , Percloratos/farmacologia , Cloreto de Sódio/farmacologia , Compostos de Sódio/farmacologia , ÁguaRESUMO
Transmission electron microscopy and scanning force microscopy of negative-stained, carbon-coated replica and mica-adsorbed preparations of 200 microM poly r(A-U) and 50 microM ethidium bromide/200 microM poly r(A-U) have been employed to evaluate ethidium-induced changes in poly r(A-U) topology. Poly r(A-U) alone exhibits elongated conformations 85-115 nm in length that possess a number of hairpin loops as well as single-stranded domains. While the double-stranded domains are found predominately at the base of the hairpin loops (diameter = 5-30 nm), other rod-like (presumably double-stranded) regions ranging from 25-80 nm in length are present in other portions of the poly r(A-U). In contrast with the poly r(A-U) alone, the EB/poly r(A-U) combination appears as a heterogeneous population of condensed structures whose lengths and widths vary from 12-88 nm and 15-45 nm, respectively. These conformational changes are due to a number of factors, including the displacement of ordered water surrounding the poly r(A-U) and charge shielding of the phosphate groups of the poly r(A-U) upon the binding of the ethidium.
Assuntos
Etídio/química , Microscopia de Força Atômica/métodos , Microscopia Eletrônica/métodos , Modelos Químicos , Poli A-U/química , RNA de Cadeia Dupla/ultraestrutura , Adenina/química , Conformação Molecular , Polímeros , RNA de Cadeia Dupla/química , Uracila/químicaRESUMO
The energetics of hydration of natural DNA of different AT/GC content and model double-helical polyribonucleotides was studied. The results obtained by a new approach, which is based on calorimetric measurements of hydration-dehydration energy of nucleic acid-water systems at different relative humidities are presented. A correlation between the dehydration energy and the nucleotide composition of native DNA was found. The energetic characteristics of systems containing deoxynucleoside monophosphates and water clusters of different dimensions were obtained by the Monte Carlo method. The results of computer simulation correlate with the experimental calorimetric data.
Assuntos
Ácidos Nucleicos/química , Nucleotídeos/química , Água/química , Calorimetria , DNA/química , Método de Monte Carlo , Poli A-U/química , Poli C/química , Poli G/química , TermodinâmicaRESUMO
Polyribonucleotide duplex poly(A).poly(U) was modified with cis-diammine dichloroplatinum (II) (cis-DDP). It was shown that the antiinfluenza protective activity of the modified duplex in mice increased with the degree of modification (rb) rising up to 0.2. The effect was different from that for poly(I).poly(C) and poly(G).poly(C). The interferon titers in the murine brain increased in parallel with increasing of the antiviral activity. It was assumed that the structural specificity of the poly(A).poly(U) duplex was responsible for the phenomenon and that cis-DDP interaction with N(7) atoms of the adenine heterocycles blocked the "abnormal" Hoogsteen pairing of adenines with uracils. As a result the antiviral activity increased because of lowering the quantity of the intramolecular defects and increasing the length of the regular double-stranded regions.