L. Ötvös
Hungarian Academy of Sciences
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Featured researches published by L. Ötvös.
Tetrahedron Letters | 1993
Janos Sagi; Attila Szemzo; Katalin Ebinger; Anna Szabolcs; Gyula Sági; Éva Ruff; L. Ötvös
Abstract Properties of oligodeoxynucleotides essential for the antisense effect can be favourably modified by substitution of the heterocyclic base moiety. This is shown here for duplex stability by 5 alkyl, 5-(1-alkenyl) and 5-(1-alkynyl) substitution of the pyrimidines in the self-complementary (dT-dA) 10 and (dC-dG) 6 oligomers as well as for the hydrophobic character of the (dT-dA) 10 series.
Tetrahedron | 1995
I. Tömösközi; Eszter Gács-Baitz; L. Ötvös
Abstract Separated P-diastereomers of H-phosphonate diesters gave exclusively one isomer of amidates on treatment with CCl 4 + butylamine with inversion of configuration. NOE experiments and the trend observed in 3 J(C2-P) and 3 J(C4-P) couplings were applied for stereochemical assignment. Separated P-diastereomers of H-phosphonate diesters gave exclusively one isomer of amidates on treatment with CCl 4 + butylamine with inversion of configuration. NOE experiment and the trend observed in 3 J(C2-P) and 3 J(C4-P) couplings were applied for stereochemical assignment
Bioorganic Chemistry | 1990
Miklós Simonyi; Gábor Maksay; Ilona Kovács; Zsuzsanna Tegyey; László Párkányi; Alajos Kálmán; L. Ötvös
Abstract In order to distinguish conformational recognition by the receptor from steric effects brought about by substituents attached to C3 of 1,4-benzodiazepines, two series of closely related compounds were tested for binding potency. Increasing size of the 3-substituent up to isopropyl decreases both the binding and its enantioselectivity. Synthesis and X-ray determination of the molecular structure of 3,3-dimethyl derivatives possessing quasi-axial methyl substituents were followed by a mathematical separation of conformational and substituent effects for quartets with successive 3-methylation [(H)2, (S)-Me, (R)-Me, (Me)2 at C3]. Results indicate a very high preference for conformation M of the ligand by the receptor (the primary reason of stereoselectivity) and a large steric hindrance resulting from the axial methyl substituent. A lower but still unexpectedly substantial steric effect is exerted by the equatorial methyl group.
Journal of Biomolecular Structure & Dynamics | 1988
Michaela Vorlíčková; Janos Sagi; Anna Szabolcs; Attila Szemzo; L. Ötvös; Jaroslav Kypr
It is demonstrated that a two-state conformational isomerization is induced in the poly(amino2-dA-dT) duplex by submillimolar concentrations of divalent magnesium cations in low-salt aqueous solution. The isomerization is fast and has a low degree of cooperativity. The resulting conformer is the unusual X-DNA double helix originally observed with poly(dA-dT) at very high concentrations of CsF. Interestingly, the X form is induced in poly(amino2dA-dT) under the physiological conditions when poly(dG-methyl5dC) assumes Z-DNA. The same conditions of stabilization are presumably connected with the fact, observed in previous phosphorus NMR studies, that Z- and X-DNA have similar polydinucleotide backbone architectures. Results presented in this work permit to specify base pair exocyclic groups responsible for the radically different conformational variability of the synthetic DNA molecules containing alternating purine-pyrimidine sequences of GC or AT base pairs.
Antimicrobial Agents and Chemotherapy | 2006
L. Ötvös; Vanessa de Olivier Inacio; John D. Wade; Predrag Cudic
ABSTRACT The antimicrobial activity of amoxicillin against TEM-1-expressing strains could be fully recovered when bacteria were preincubated with sublethal doses of an antibacterial peptide derivative. Assays with the simultaneous administration of antibiotics or synergy assays with kanamycin or ciprofloxacin, where resistance development does not involve properly folded proteins, failed to yield similar results.
International Journal of Biological Macromolecules | 1991
Janos Sagi; Attila Szemzo; L. Ötvös; Michaela Vorlíčková; Jaroslav Kypr
The B-to-Z conformational transition of poly(dG-dC) is highly promoted by 5-methyl substitution of the dC moiety, i.e. in poly(dG-methyl5dC). By the synthesis of a new poly(dG-dC) analogue, poly(dG-ethyl5dC), the effect of a longer alkyl-chain substituent of dC on structure and conformation has been studied with ultraviolet absorption melting profiles and circular dichroism spectroscopy. The 5-ethyl substituent in poly(dG-ethyl5dC) destabilizes the duplex structure against thermal denaturation compared with both poly(dG-methyl5dC) and poly(dG-dC). C.d. studies also reveal that for the high-salt B-Z transition of poly(dG-ethyl5dC) a higher NaCl concentration is required than for that of poly(dG-methyl5dC), although much lower than for poly(dG-dC). However low-salt Z-DNA in poly(dG-ethyl5dC) shows unique features, e.g. it needs no divalent cations to be stable. The low-salt B-Z transition of poly(dG-ethyl5dC) can also be observed by the absorption-temperature melting profile, in contrast to both poly(dG-methyl5dC) and poly(dG-dC). The effects of MgCl2 concentration, temperature, acid pH and trifluorethanol on the conformation of poly(dG-ethyl5dC) have also been determined.
Nucleosides, Nucleotides & Nucleic Acids | 1999
L. Ötvös; Janos Sagi; Gy. Sági; A. Szemz
Abstract The effect of pyrimidine base substitution on the sensitivity of oligonucleotides to nucleases has been studied with two series of self complementary deoxyoligonucleotides containing n-alkyl, n-(1-alkenyl) or n-(1-alkynyl) groups at C5 of pyrimidines, (dA-r5dU)10 and (dG-rsdC)6. The rate of hydrolysis by snake venom phosphodiesterase and in human serum decreased with increasing length and unsaturation of the substituent.
International Journal of Biological Macromolecules | 1987
Michaela Vorlíčková; Jaroslav Kypr; Janos Sagi; L. Ötvös; Vladimír Sklenář
Abstract This work compared circular dichroism and phosphorus n.m.r. of poly(dA-dU)·poly(dA-dU), poly(dA-dT)·poly(dA-dT), poly(dA-ethyl 5 dU)·poly(dA-ethyl 5 dU), and poly(dA-butyl 5 dU)·poly(dA-butyl 5 dU) at low-salt and in concentrated caesium chloride and caesium fluoride solutions. It is demonstrated that growing bulk of the substituent increases the conformationl anomaly residing in the purine(3′–5′)pyrimidine steps while the backbone is less affected in the pyrimidine (3′–5′)purine steps. As the length of the substituent increases, conformation of the polynucleotides alters more dramatically at increasing concentrations of caesium cations. At high CsF concentrations, all the polynucleotides adopt a novel conformer which we call X-DNA and its formation is promoted by larger substituents. The X-DNA conformation of poly(dA-butyl 5 dU)·poly(dA-butyl 5 dU) gives two phosphorus n.m.r. resonances separated as much as in the case of the left-handed zig-zag Z-DNA double helix of poly(dG-dC)·poly(dG-dC) but X-DNA and Z-DNA differ qualitatively by an opposite dinucleotide repeat. Phosphorus n.m.r. spectra of poly(dA-dT)·poly(dA-dT) and poly(dA-butyl 5 dU)-poly(dA-butyl 5 dU) differ quantitatively at high CsF concentrations, which may reflect conformational variability of the X-DNA backbone. Poly(dA-butyl 5 dU)·poly(dA-butyl 5 dU), but not poly(dA-ethyl 5 dU)·poly(dA-ethyl 5 dU) and the related polynucleotides with shorter substituents in position 5 of uracil, exhibits one more reversible transition at very high caesium fluoride concentrations. It is accompanied by polynucleotide associations and has a slow kinetics. This transition may involve one more radical change in the double helix architecture from X-DNA into another conformation.
Hormone Molecular Biology and Clinical Investigation | 2015
Eva Surmacz; L. Ötvös
Abstract Obesity is a significant risk factor for the development of different cancer types and has been associated with poorer response to oncotherapies and linked to earlier recurrence of the neoplastic disease. While molecular mechanisms of these associations are still under investigation, functional dysregulation of two major fat tissue-derived adipokines, leptin and adiponectin, appears to play an important role. Leptin is known to activate carcinogenic pathways, while adiponectin appears to exert antineoplastic activities and interfere with leptin-induced processes. Because excess body fat is associated with increased leptin expression and adiponectin downregulation, therapeutic rebalancing of these pathways may benefit cancer patients, especially the obese subpopulations. This review focuses on our novel leptin receptor antagonists and adiponectin receptor agonists designed for therapeutic modulation of obesity-associated pathways in cancer.
Tetrahedron | 1989
J. Béres; Gy. Sági; Eszter Baitz-Gács; I. Tömösközi; Lajos Gruber; L. Ötvös
Abstract Stereospecific synthesis of (−)-carba-3′-deoxy-3′-fluorothymidine (−)- 11 is reported from the protected (−)-carbocyclic 3′-epi-thymidine (−)- 7 using diethylaminosulfur trifluoride. Under the conditions used, extensive dehydration of the blocked precursor into 10 and formation of the 4′-fluoro analogue ( 9 ) were also observed. An attempted simplification of our methodology based on (+)-(1R, 5S)-2-oxabicyclo[3.3.0]oct-6-en-3-one failed, but a novel cyclopentane ( 2 ) ring expansion to tetrahydropyran ( 18 ) was discovered.