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1.
Front Vet Sci ; 11: 1396871, 2024.
Article in English | MEDLINE | ID: mdl-38659446

ABSTRACT

Accessory canals and apical deltas have been extensively studied in human dentistry. Their clinical role as a difficult to clean reservoir for bacteria during endodontic treatments has been well described. Many papers describe in detail the pulp anatomy of equine dentition but little attention has been given to their apical ramifications. The goal of this paper is to describe the presence and anatomy of these accessory canals and apical deltas in healthy equine cheek teeth and discuss their possible relevance in the light of equine endodontics. To accomplish this, 15 maxillary and 19 mandibular healthy cheek teeth were collected ranging from Triadan 06 s to 11 s with eruption ages from 4 to 9 years. Their root anatomy was documented in detail based on micro computed tomography images. A subset of 3 teeth also underwent histological examination. Accessory canals were found in all but two teeth examined. Up to 44 accessory canals per tooth have been found with locations ranging from the root furcation down to the apex of the root and with highly variable diameters. Apical deltas in different stages of development were found in 84% of the roots. The presence of accessory canals identified on microCT images could be confirmed using histological examination although some of them were obliterated by reparative dentin. Accessory canals can be found in most equine cheek teeth and add complexity to their endodontic anatomy. This could have important implications for their treatment in case of pulp pathology. In humans, failure to remove bacterial biofilm from such canals has been associated with failure of endodontic treatment. Research on diseased equine teeth is required to gain a better understanding of their clinical relevance in horses.

2.
Front Psychol ; 15: 1283115, 2024.
Article in English | MEDLINE | ID: mdl-38680277

ABSTRACT

Background: The aim of the present study is to translate the Grit questionnaire into Hungarian and validate specifically within the context of sports. The second goal is to assess the questionnaire in Hungarian as a pilot study in the athlete population and to compare the grit trait with the coaches' athlete evaluation. Methods: Two hundred and sixty nine athletes, including 40 national team players, took part in the study, with an average age of 18.17 years (SD = 5.51). For the preliminary assessment, the Cloninger Temperament and Character Questionnaire (TCI-RH) was used; the coaches' athlete evaluation was modeled on a talent map. Results: The confirmatory factor analysis confirmed the fit of the two-factor structure, and the internal reliability of the questionnaire scales also proved to be adequate. 2. There is no relationship between adolescents' perceived grit and coach ratings. 3. The national team players achieved a higher grit score. Conclusion: Based on the psychometric indicators, the validity and reliability of the questionnaire proved to be adequate. Therefore, it is applicable and useful for psychological practitioners and researchers in the Hungarian population within the context of sports.

4.
Arch Sex Behav ; 53(2): 811-837, 2024 02.
Article in English | MEDLINE | ID: mdl-38127113

ABSTRACT

The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.


Subject(s)
Sexual Behavior , Sugars , Humans , Male , Female , Interpersonal Relations , Sex Characteristics , Attitude
5.
Psychiatry Res ; 292: 113323, 2020 10.
Article in English | MEDLINE | ID: mdl-32736268

ABSTRACT

Previous research warned that internet and social media use could have a negative effect on the social lives of excessive users. Based on the social compensation hypothesis, however, factors related to social fears could lead to problematic social networking site (SNS) use because individuals try to compensate for their offline popularity. It was shown that individuals with higher levels of social fears tend to prefer computer-mediated (CMC) instead of face to face (FTF) communication. Here, we aimed to create a model that shows the direct and indirect effects of social anxiety and self-esteem on problematic SNS use. A total of 215 participants filled out our survey including measures of social anxiety, self-esteem, fear of negative evaluation, social media and Internet addiction. Using structural equation modeling we tested the indirect and direct effects between the variables. Our results indicated that social anxiety and lower self-esteem could lead to favoring CMC over FTF communication, which may result in problematic internet (PIU) and SNS use as a compensatory behavior to cope with fear of negative evaluation. The indirect pathways might highlight relevant differences behind the motivation of PIU - anonymity - and problematic SNS use - control. Theoretical as well as practical implications are discussed.


Subject(s)
Anxiety/psychology , Fear/psychology , Latent Class Analysis , Self Concept , Social Media/trends , Social Networking , Adaptation, Psychological/physiology , Adult , Aged , Aged, 80 and over , Anxiety/diagnosis , Behavior, Addictive/diagnosis , Behavior, Addictive/psychology , Female , Humans , Internet/trends , Male , Middle Aged , Motivation , Surveys and Questionnaires , Young Adult
6.
Psychiatry Res ; 291: 113223, 2020 09.
Article in English | MEDLINE | ID: mdl-32563747

ABSTRACT

The Spielberger State-Trait Anxiety Inventory (STAI) has been widely used to measure the state and trait components of anxiety. We sought to develop a short, yet reliable and valid form of these scales for use in circumstances where the full-form is not feasible. We abbreviated the scales using item response theory analyses to retain the items that could discriminate the best among participants. One sample (N = 922) completed the state scale, a second sample (N = 2227) completed the trait scale, while a third sample (N = 250) completed the short forms. Our participants completed the Hungarian version of STAI alongside other measures to observe external validity. We calculated cut-off scores for the state (>9.5,) and trait (>13.5) scales. A total of 19.5% and 20.1% of the respondents reached the cut-off scores. The five-item short forms of STAI had sound psychometric properties that are comparable to those obtained on the full-form. The external validity of the scales is also demonstrated. We report detailed descriptive statistics that could be used in further studies as standards. The short scales are reliable measures that could be used in clinical screening and behavioural research; especially where practical considerations preclude the use of a longer questionnaire.


Subject(s)
Anxiety/diagnosis , Anxiety/psychology , Psychiatric Status Rating Scales/standards , Psychometrics/standards , Self Report/standards , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Mass Screening/methods , Mass Screening/standards , Mass Screening/trends , Middle Aged , Psychometrics/methods , Psychometrics/trends , Reproducibility of Results , Surveys and Questionnaires/standards , Young Adult
7.
Psychiatr Hung ; 34(1): 11-18, 2019.
Article in Hungarian | MEDLINE | ID: mdl-31074419

ABSTRACT

INTRODUCTION: One of the most common mental disorders is the specific phobia. Within this, the prevalence of animal phobia, such as the fear from spiders and snakes, is very high. In case of irrational fears, beyond the change in behavior (for example avoidance of the situation), a specific brain activation pattern can also be observed. However, if animal phobia is detected, it can be treated through several different therapeutic methods. There is a great need for reliable questionnaires to examine the subtypes of animal phobia. The SNAQ-12 and SPQ-12 can be used for this purpose, furthermore these questionnaires have good psychometric properties and clinical cut-off scores. The aim of the present study is therefore to examine the psychometric properties of the two questionnaires' Hungarian version. METHOD AND RESULTS: The SNAQ-12 (12 item long Snake Questionnaire, SNAQ) and the SPQ-12 (12 item long Spider Phobia Questionnaire), according to the measured sample (1071 Hungarian subject) have excellent psychometric properties (Snake Questionnaire: Cronbach alpha=0.912. Spider Questionnaire: Cronbach alpha=0.909), and are suitable for reliable testing of fear from snake and spider. CONCLUSION: The questionnaires are useful in phobia related researches and studies and can promote the clinical work, to recognize phobias and to monitor the effectiveness of therapy.


Subject(s)
Phobic Disorders , Snakes , Spiders , Animals , Humans , Hungary , Surveys and Questionnaires
8.
Pancreatology ; 10(4): 483-90, 2010.
Article in English | MEDLINE | ID: mdl-20720450

ABSTRACT

AIMS: Bacterial translocation from the intestinal tract plays an important role in severe acute pancreatitis (AP). Human ß-defensins are a family of antimicrobial peptides present at the mucosal surface. The aim of this study was to investigate the relevance of single nucleotide polymorphisms (SNPs) in the DEFB1 gene and copy number polymorphisms of the DEFB4 genes in AP. METHODS: 124 AP patients (30 with mild and 94 with severe disease) and 100 healthy controls were enrolled in the study. Three SNPs of the DEFB1 gene [G-20A (c.-20G→A), C-44G (c.-44C→G) and G-52A (c.-52G→A)] were genotyped by Custom TaqMan assay. The DEFB4 gene copy number was determined by means of a TaqMan real-time PCR assay. RESULTS: Significantly higher frequencies of the AA genotype of G-20A (c.-20G→A) and the AA genotype of G-52A (c.-52G→A) were observed among the patients with severe AP (SAP) compared with the healthy controls (38 vs. 20 and 41 vs. 18%, respectively). The GG protective genotype of C-44G (c.-44C→G) SNP was much less frequent (1%) among the patients than among the controls (9%). A higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with SAP compared with the healthy controls (62 vs. 24%, respectively). CONCLUSIONS: The variations in the genes encoding human ß-defensin-1 and -2 may be associated with the risk of SAP. and IAP.


Subject(s)
DNA Copy Number Variations , Genetic Predisposition to Disease , Pancreatitis, Acute Necrotizing/genetics , Polymorphism, Single Nucleotide , beta-Defensins/genetics , Amylases/blood , Female , Gene Dosage , Genotype , Humans , Male , Middle Aged , Pancreatitis, Acute Necrotizing/blood , Pancreatitis, Acute Necrotizing/pathology , Risk Factors , beta-Defensins/blood
9.
Pancreatology ; 9(4): 383-91, 2009.
Article in English | MEDLINE | ID: mdl-19451748

ABSTRACT

AIMS: High-mobility group box protein 1 (HMGB1), a late-acting proinflammatory cytokine, is secreted actively by inflammatory cells, and released passively from necrotic cells. From the aspect that both inflammation and necrosis are involved in the pathogenesis in acute pancreatitis, the aim of the study was a joint investigation of the plasma concentrations of HMGB1, its soluble receptor for advanced glycation end-products (sRAGE), and the circulating DNA as a marker of cell death. METHODS: 62 patients with acute pancreatitis (30 mild, 32 severe), 20 patients with sepsis, and 20 healthy controls were enrolled in the study. HMGB1 and sRAGE plasma levels were measured by means of ELISA. Plasma DNA concentrations were estimated by real-time quantitative PCR for the beta-globin gene. RESULTS: The circulating HMGB1 level was significantly higher in patients with severe acute pancreatitis (13.33 +/- 2.11 ng/ml) than in healthy controls (0.161 +/- 0.03 ng/ml) or than in patients with mild pancreatitis (2.64 +/- 0.185 ng/ml). The plasma concentration of sRAGE was highest in patients with sepsis (2,210 +/- 252 pg/ml), while the levels of sRAGE correlated inversely with that of HMGB1 in patients with acute pancreatitis. The plasma DNA level was significantly elevated in patients with severe acute pancreatitis (2,206 +/- 452 ng/ml). CONCLUSION: A complex study of the plasma levels of HMGB1, sRAGE and circulating DNA can be informative in evaluations of acute pancreatitis with different levels of severity.


Subject(s)
DNA/blood , HMGB1 Protein/blood , Pancreatitis/blood , Receptors, Immunologic/blood , Acute Disease , Female , Glycation End Products, Advanced/blood , Humans , Male , Middle Aged , Receptor for Advanced Glycation End Products , Sepsis/blood , beta-Globins/genetics
10.
J Biomol Struct Dyn ; 12(5): 1121-7, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7626244

ABSTRACT

The interaction between polynucleotides: poly(dA)-poly(dT), poly(dA-dT), poly(am2dA-dT), and the AT-specific compounds of benzimidazol group has been studied. It is been shown that these compounds bind to poly(dA)-poly(dT) and poly(dA-dT) at low and high salt concentration in solution. Poly(am2dA-dT) interacts with AT-specific compounds only at low salt, where this polynucleotide is in a B-form, but not at high salt, when the polynucleotide converts to another conformation. Thus, the interaction specificity of the groove-binding ligands is influenced not only by the minor groove substituents, but the peculiarities of the secondary structure of polynucleotides.


Subject(s)
Benzimidazoles/chemistry , Poly dA-dT/chemistry , Benzimidazoles/chemical synthesis , Benzimidazoles/metabolism , Circular Dichroism , Hydrogen Bonding , Osmolar Concentration , Poly dA-dT/metabolism , Sodium Chloride
11.
Acta Pharm Hung ; 63(4): 204-14, 1993 Jul.
Article in Hungarian | MEDLINE | ID: mdl-8379336

ABSTRACT

5-Isopropyl-2'-deoxyuridine is the active ingredient of Hevizos ointment, a commercially available drug in Hungary, applied on the local treatment of patient with herpes labialis, zoster and progenitalis. The 5'-triphosphate derivative of the compound was incorporated by a DNA polymerase enzyme into a synthetic DNA of poly(dA-dT) type in order to study possible alterations in the structure and bioorganic functions of the DNA, in comparison with unmodified poly(dA-dT). Alterations observed by spectroscopic, electron microscopic and biochemical methods refer to the formation of stable hairpins protruding from the DNA duplex, which may be responsible for the impairment of the integrity of the DNA structure. This, in turn, may negatively influence normal biochemical functions of a DNA.


Subject(s)
Antiviral Agents/chemistry , DNA/chemistry , Deoxyuridine/analogs & derivatives , Poly dA-dT/chemistry , Antiviral Agents/metabolism , Deoxyuridine/chemistry , Deoxyuridine/metabolism , Microscopy, Electron , Molecular Structure , Nucleic Acid Conformation , Ointments , Poly dA-dT/metabolism
12.
J Biomol Struct Dyn ; 10(4): 681-92, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8466673

ABSTRACT

We have synthesized poly(dA,dPu-dT) and poly(dA,n2dPu-dT) containing, respectively, 5.7% of purine and 7.4% of amino2purine in place of adenine to demonstrate that these apparently negligible perturbations of the primary structure have dramatic consequences for the polynucleotide conformational isomerizations. The replacement of adenine by amino2purine, preserving the number of hydrogen bonds between the complementary bases, has a stronger effect on the polynucleotide conformational isomerizations than the replacement with purine that is bound only by a single hydrogen bond to thymine. Nevertheless, poly(dA,dPu-dT) forms a more thermostable duplex than poly(dA,n2dPu-dT). Furthermore the few amino2purines in poly(dA,n2dPu-dT) inhibit its isomerization into X-DNA, stabilize but modify A-DNA and stabilize Z-DNA. Kinetics of the B-Z transition of poly(dA,n2dPu-dT) is fast to indicate that the amino groups in the double helix minor groove substantially decrease the kinetic barrier between B- and Z-DNA. On the other hand, the replacement of adenine by purine destabilizes both Z-DNA and A-DNA, and the destabilization of X-DNA is weaker than with amino2purine. A-form and B-form perhaps coexist in poly(dA,dPu-dT) at high concentrations of ethanol.


Subject(s)
Adenine/chemistry , DNA/chemistry , Nucleic Acid Conformation , Poly dA-dT/chemistry , Purines/chemistry , Aminopyrine/chemistry , Hydrogen Bonding , Spectrophotometry, Ultraviolet , Stereoisomerism
13.
Arch Biochem Biophys ; 286(1): 1-5, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1897940

ABSTRACT

2,2'-Anhydro-3'-deoxy-5-ethyluridine, a new pyrimidine nucleoside analog, has been examined in terms of its binding potency to uridine phosphorylase, and its conformation in solution (NMR) was studied. 2,2'-Anhydro-3'-deoxy-5-ethyluridine has a Ki value of 3.4 microM for uridine phosphorylase from rat intestinal mucosa. This value is approximately one order of magnitude lower than the Km for uridine (22 microM), the natural substrate. The presence of the 3'-OH group (in the ribo-configuration) on pyrimidine nucleoside analogs may not be considered a prerequisite for the binding to uridine phosphorylase; however, it enhances the binding in the case of flexible ligands cooperating in the process of conformation change toward a more favorable enzyme-ligand interaction. The presence of the 3'-OH group in pyrimidine nucleosides seems to be essential if the molecule is to become a substrate.


Subject(s)
Deoxyuridine/analogs & derivatives , Uridine Phosphorylase/metabolism , Uridine/analogs & derivatives , Uridine/metabolism , Animals , Deoxyuridine/metabolism , Intestinal Mucosa/enzymology , Kinetics , Magnetic Resonance Spectroscopy/methods , Molecular Conformation , Molecular Structure , Rats , Uridine/chemical synthesis , Uridine/chemistry , Uridine Phosphorylase/antagonists & inhibitors , Uridine Phosphorylase/isolation & purification
14.
Xenobiotica ; 21(3): 359-69, 1991 Mar.
Article in English | MEDLINE | ID: mdl-1650515

ABSTRACT

1. [E]-5-(2-bromovinyl)-2,2'-anhydrouridine [( E]BVANUR) has considerable antiviral activity against herpes simplex virus type 1 (HSV-1). 2. [E]BVANUR is not a substrate of pyrimidine nucleoside phosphorylases, but it is an inhibitor of uridine phosphorylase (Ki = 450 nM). 3. [E]BVANUR (trans-isomer, parent compound) undergoes isomerization to [Z]BVANUR (cis-isomer), the only metabolite in rat, which was identified by h.p.l.c., mass spectra and n.m.r. spectroscopy. 4. Absorption of the drug from the gastrointestinal tract after oral administration is minimal. Absorption of [E]BVANUR from the abdominal cavity after i.p. administration was slow.


Subject(s)
Antiviral Agents/metabolism , Uridine/analogs & derivatives , Vinyl Compounds , Animals , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Autoradiography , Biotransformation , Bromodeoxyuridine/analogs & derivatives , Bromodeoxyuridine/metabolism , Bromodeoxyuridine/pharmacokinetics , Bromodeoxyuridine/pharmacology , Chromatography, High Pressure Liquid , Isomerism , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Rats , Rats, Inbred Strains , Simplexvirus/drug effects , Spectrophotometry, Ultraviolet , Tissue Distribution , Uridine/pharmacokinetics , Uridine/pharmacology , Vinyl Compounds/pharmacokinetics , Vinyl Compounds/pharmacology
16.
Biochem Pharmacol ; 39(7): 1247-53, 1990 Apr 01.
Article in English | MEDLINE | ID: mdl-2138895

ABSTRACT

2,2'-Anhydro-5-ethyluridine (ANEUR), a potent inhibitor of uridine phosphorylase, markedly potentiated the antitumor activity of fluorouridine (FUR) against murine mammary adenocarcinoma 755 in BDF1 mice and human colon adenocarcinoma LS174T in athymic-nude mice. Whereas ANEUR annihilated the antitumor activity of 5-fluoro-2'-deoxyuridine (FUdR) and 5'-deoxy-5-fluorouridine (DFUR) in the murine adenocarcinoma 755 system, it did not alter the antitumor activity of FUdR in the human adenocarcinoma LS174T system. In vitro, ANEUR proved inhibitory to the phosphorolytic cleavage of both FUR and FUdR by uridine phosphorylase, and this could explain why in vivo conversion of FUR and FUdR to 5-fluorouracil was suppressed. FUR can be held directly responsible for the antitumor effects observed in the murine adenocarcinoma 755 system, whereas in the activity against human adenocarcinoma LS174T may be mediated by both FUR and FUdR.


Subject(s)
Adenocarcinoma/drug therapy , Colonic Neoplasms/drug therapy , Floxuridine/therapeutic use , Mammary Neoplasms, Experimental/drug therapy , Pentosyltransferases/antagonists & inhibitors , Uridine Phosphorylase/antagonists & inhibitors , Uridine/analogs & derivatives , Adenocarcinoma/pathology , Animals , Colonic Neoplasms/pathology , Drug Interactions , Floxuridine/blood , Fluorouracil/blood , Humans , Kinetics , Male , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Nude , Neoplasm Transplantation , Thymidine Phosphorylase/antagonists & inhibitors , Tumor Cells, Cultured/drug effects , Uridine/blood , Uridine/pharmacokinetics , Uridine/pharmacology , Uridine/therapeutic use
17.
Acta Paediatr Hung ; 30(2): 309-16, 1990.
Article in English | MEDLINE | ID: mdl-2174249

ABSTRACT

The hydroxyl radical scavenging capability of vinpocetine was studied in vitro by aromatic hydroxylation and deoxyribose degradation methods. Hydroxyl radicals were generated by the Fenton reaction. The effect of vinpocetine was compared to other antioxidants, to mannitol, vitamin E and dimethyl sulfoxide. The antioxidant capacity of vinpocetine is near to vitamin E, and higher than that of mannitol.


Subject(s)
Free Radical Scavengers , Vinca Alkaloids/pharmacology , Antioxidants/pharmacology , Deoxyribose , Free Radicals , Hydroxides , Hydroxyl Radical , Hydroxylation
18.
J Biomol Struct Dyn ; 6(3): 503-10, 1988 Dec.
Article in English | MEDLINE | ID: mdl-3271535

ABSTRACT

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.


Subject(s)
DNA , Polydeoxyribonucleotides , Circular Dichroism , Isomerism , Magnetic Resonance Spectroscopy , Nucleic Acid Conformation , Viruses/genetics
19.
Eur J Biochem ; 178(1): 173-81, 1988 Dec 01.
Article in English | MEDLINE | ID: mdl-3203686

ABSTRACT

Some 3'- and/or 5'-substituted pyrimidine nucleosides, as well as anhydropyrimidine nucleosides, which have no flexibility about the N-glycosidic bond were studied as inhibitors of thymidine phosphorylase and uridine phosphorylase. The conformation of some analogs was also investigated in order to obtain information on substrate binding to the enzyme. The above compounds, including the potential anti-(human immunodeficiency virus) agent, 3'-azido-2',3'-dideoxy-5-methyluridine were not substrates for either thymidine phosphorylase or uridine phosphorylase. (The only exception was arabinofuranosyl-5-ethyluracil, which proved to be a poor substrate for uridine phosphorylase). The phosphorolysis of thymidine by thymidine phosphorylase was slightly or not at all altered by these pyrimidine nucloside analogs. The lowest Ki was obtained in the case of 3'-azido-2',3'-dideoxy-5-methyluridine and the highest in the case of 2'-deoxylyxofuranosyl-5-ethyluracil, when studying the analogs with flexible structure as inhibitors of uridine phosphorylase. The Ki for 2,3'- and 2,5'-anhydro-2'-deoxy-5-ethyluridine was 5-6 orders of magnitude higher than that for 2,2'-anhydro-5-ethyluridine. Competitive inhibition was observed in all cases. For these three molecules computer-aided molecular modelling predicts the following glycosidic torsion angles chi (O4,-C1,-N1-C2): 109 degrees for 2,2'-anhydro-5-ethyluridine, and 78 degrees and 71 degrees for 2,3'- and 2,5'-anhydro-2'-deoxy-5-ethyluridine respectively. These values are corroborated by high-resolution 13C- and 1H-NMR studies. 2'-Deoxy-5-ethyluridine is predicted to have a syn conformation with chi = 46 degrees and delta E about 2.5 kJ/mol over the minimum energy (in anti position, chi = -147 degrees). 1H and 13C data including homonuclear Overhauser enhancements complete the information about the solution conformation. Considering the Ki values obtained, it is likely that substrates of uridine phosphorylase will bind to the enzyme in the same conformation as 2,2'-anhydro-5-ethyluridine. The greater than 30 degrees deviation from the N-glycosidic torsion angle of 2,2'-anhydro-5-ethyluridine results in much higher Ki values.


Subject(s)
Pentosyltransferases/antagonists & inhibitors , Pyrimidine Nucleosides/pharmacology , Uridine Phosphorylase/antagonists & inhibitors , Animals , Binding Sites , Computer Simulation , Energy Transfer , Glycosides/analysis , Intestinal Mucosa/enzymology , Magnetic Resonance Spectroscopy , Protein Conformation , Rats , Solutions , Substrate Specificity
20.
Nucleic Acids Res ; 16(1): 279-89, 1988 Jan 11.
Article in English | MEDLINE | ID: mdl-3340526

ABSTRACT

It has previously been demonstrated by other workers that the duplex of a synthetic DNA poly(amino2dA-dT) undergoes a salt-induced conformational isomerization. We show in the present work using circular dichroism that the same isomerization is induced in poly(amino2dA-dT) by various alcohols. The isomerization was originally identified as the B-to-Z and then B-to-A conformational transition of DNA but we demonstrate that the high-salt or alcohol conformation of poly (amino2dA-dT) is the non Z-DNA zig-zag double helix we have previously observed with poly(dA-dT) and called X-DNA. X-DNA is a cesium cation specific conformation of poly(dA-dT) while no similar cation specificity is observed with poly(amino2dA-dT). Thus it appears that the extra amino group attached to A and cesium cations make the same thing; they probably dehydrate the double helix minor groove and relieve its conformational variability. Poly(amino2dA-dT) is exceptionally stable in X-DNA and conditions inducing it are mild, which opens the door to assess its molecular structure.


Subject(s)
DNA , Nucleic Acid Conformation , Polydeoxyribonucleotides , Circular Dichroism , Ethanol , Hypertonic Solutions , Poly dA-dT , Solutions
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