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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 30 (1990), S. 116-124 
    ISSN: 1432-1432
    Keywords: Thermodynamic model of DNA base pairs ; Mutation-selection equilibrium ; Directional mutation pressure ; Optimons ; Rate of mutation ; Substitution mutations ; Mismatches ; Rare tautomers ; Tautomerizing proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An inherent feature of double-stranded DNA is the possible replacement of any base pair by another one upon replication. A replication-dependent substitution mutation of a matched base pair requires the temporary formation of a mismatched base pair (mispair). A functionally complementary pair of mispairs is ascribed to each of the four types of substitution mutations. Provided that all types of mispairs can be formed, a dynamic biological equilibrium between the four matched base pairs must exist in all DNA, which is directly related to the formation and stability of the corresponding eight mispairs in vivo. Each nucleotide position in a genome can therefore be described as a system of six dynamic equilibria between the four matched base pairs. After a sufficient number of replications, these equilibrium states will express an overall mutation-selection balance for each individual base pair. In a thermodynamic context, the mispairs represent intermediate states on the transformation pathway between the matched base pairs. Catalysts change the stability and probability of formation of intermediate states. Mutagenic proteins are proposed as hypothetical substitution mutation catalysts in vivo. Functionally, they would be capable of recognizing a particular DNA sequence, tautomerizing a nucleotide base thereof, and hence efficiently inducing a specific misincorporation. Phenomenologically such catalysts would accelerate the rates of substitution mutations and provide pathways for directional mutation pressure.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2′,3′-O-Isopropylidene-5-methyl(15N2)[O2,O4-17O2]uridine (= 2′,3′-O-isopropylidene (15N2)[O2,O4-17O2]-ribosylthymine; 1) was analyzed by 15N-and 17O-NMR spectroscopy. The 15N and 17O chemical shifts revealed, in the absence and presence of unlabelled 2′,3′-O-isopropylideneadenosine (2), the formation of thymine-thymine and thymine-adenine base pairs in CHCl3. As expected, cyclic complexes stabilized by two H-bonds occurred at low temperatures, but at elevated temperatures, the data suggest that open complexes involving only one H-bond prevailed. The 17O-NMR data showed the cyclic thymine-adenine pair in a reverse base pair geometry. The open base pair involved contacts to the urea-derived carbonyl O-atom of thymine. The thermodynamics of complex formation of the cyclic and open forms in both homo and hetero pairs were calculated from the temperature and concentration dependence of the 15N-NMR data using a new method. It involves a fitting procedure onto the experimental isotherms using a theoretically derived function with the standard Gibbs free energy as a parameter to be optimized. ΔH° and ΔS° were derived from a linear regression of ΔG°(T) vs. T. The fitting procedure circumvents the baseline problem and could be automated and used to calculate correct thermodynamics from UV-monitored melting curves of oligonucleotides. Since titrations are not involved, this dilution method should also be a useful alternative for stability studies of supramolecular complexes in H2O and in organic solvents.
    Additional Material: 16 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A procedure was developed for the biosynthetic preparation of 15N-labelled guanosine and inosine through the action of a mutant Bacillus subtilis strain. Crude [N2,1,3,7,9-15N]guanosine and [1,3,7,9-15N]inosine were isolated from the culture filtrate by precipitation and anion-exchange chromatography (Scheme 1). No cell lysis and no enzymatic degradation was necessary. The per-isobutyrylated derivatives 1 and 2 were isolated from a complex mixture, purified by virtue of their different lipophilicity, and separated in three steps involving normal-and reversed-phase silica-gel chromatography. One litre of complex nutrient medium yielded 8.44 mmol of guanosine derivative and 2.84 mmol of inosine derivative with high average 15N enrichment (83.5 and 91.9 atom-%, resp.). [N6,1,3,7,9-15N]Adenosine (4) was obtained from 2′,3′,5′-tri-O-isobutyryl[1,3,7,9-15N]inosine (1) through the ammonolysis of its 1,2,4-triazolyl derivative with aqueous 15NH3 (Scheme 2).
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 75 (1992), S. 1078-1084 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Coprine (1), a toxine of the mushroom Coprinus atramentarius, was synthesized starting from the 2-amino and 1-carboxy-protected L-glutamic acids 4 and 12. Compound 4 was first decarboxylated by a radical chain reaction to bromide 5 which underwent ring closure to cyclopropanecarboxylate 6 on treatment with NaH (Scheme 1). Subsequent oxidative electrolysis of 7 to form tert-butyl N-(1-ethoxycyclopropyl)carbamate (8) and acidic hydrolysis yielded the 1-aminocyclopropanol hydrochloride (9). Selective cleavage of the amino-protecting group of 8 (→ 10 or 11), coupling of the corresponding amine 13 with L-glutamic acid 12, and acidic hydrolysis of the resulting L-glutamine derivative 17 yielded O-ethylcoprine (3) and coprine (1).
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 79 (1996), S. 244-254 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general synthetic approach for the synthesis of 15N- and 17O-doubly labelled pyrimidine nucleosides is described. The 15N isotopes in uridine and the 17O isotope in the urea-derived carbonyl group of uridine and cytidine originate from (15N2)[17O]urea (5) which was synthesized from 15NH4Cl, thiophosgene (1), and H2[17O]. The third 15N isotope of cytidine in 4-position stems from the substitution of the 1,2,4-triazole moiety of (15N2)[O2-17O]uridine derivative 8a/b with 15NH4OH. Hydrolysis of the same key intermediate 8a/b with Na[17O]H/H2[17O] introduced the second 17O isotope into the 4-position of uridine. The 15N- and 17O-NMR spectra of the target compounds 12 and 14 in phosphate-buffered H2O serve as references for heteronuclear NMR spectra of labelled RNA fragments.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereo- and regiochemical course in the [2+4]cycloaddition of the chiral alkylidene malonic ester 1 to selected derivatives of (2E, 4E)-4-methyl-2, 4-hexadien-l-ol (2) and (2E, 4E)-4-methyl-2, 4-hexadien-l-al (12) has been investigated. The results are discussed on the basis of semiquantitative PMO theory.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 69 (1986), S. 1041-1051 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (2S,4S)-2-(tert-Butyl)-5-oxo-1,3-dioxolan-4-acetic acid (1) was dilithiated to the enolate 2 in toluene and THF with lithium diisopropylamide (LiN(i-Pr)2) under various conditions. Deuteration experiments with 2 showed that two different stable forms of the enolate could be produced, depending on whether the deprotonation of 1 had been carried out in toluene or THF. The generated (i-Pr)2NH was coordinated to the enolate and, hence, served as a strong lipophilic solvating agent. LiN(i-Pr)2 could substitute the amine ligands of the two species to a different extent. THF was partially able to displace (i-Pr)2NH that solvated the species produced in toluene, but the coordination of the amine to the one produced in THF was quantitive. Correlations with given explanations are made.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 78 (1995), S. 1106-1111 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 5-methyl(15N2)[O2,O4-17O2]uridine (= (15N2)[O2,O4-17O 2]ribosylthymine; 15) was synthesized and analyzed by 15N- and 17O-NMR spectroscopy. (15N2)Urea was condensed with 2,3-dibromo-2-methylpropanoyl chloride (3) and cyclized to form (15N2)thymine (5). After glycosidation, the 17O isotopes were introduced in two separate steps: hydrolytic ring opening of 2,5′-anhydro derivative 9 and hydrolysis of 3-nitro-1H-1,2,4-triazole derivative 12 with labelled water in the presence of a strong base. The 15N- and 17O-NMR spectra (Fig.) of 15 in phosphate-buffered water serve as references for heteronuclear NMR spectra of labelled RNA fragments.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für die chemische Industrie 102 (1990), S. 37-59 
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Prinzipien der Replikationsgenauigkeit von Genomen werden auch heute noch nicht ganz verstanden. Für die Basen der Desoxyribonucleotide gilt die Regel nach Watson und Crick; sie erklärt, warum die Paarung der Basen Guanin und Cytosin sowie Adenin und Thymin thermodynamisch etwa hundertmal günstiger ist als die Bildung aller anderen Kombinationen. In vitro verringern Polymerasen die Bildung von Basenpaaren, die nicht den Watson-Crick-Regeln entsprechen, auf ca. 10-6 pro Watson-Crick-Basenpaar. In vivo läßt sich die Replikationsgenauigkeit auf eine Mutationswahrscheinlichkeit von ca. 10-10 erhöhen, wenn dank Polymerisations-Hilfsproteinen und DNA-Reparaturenzymen optimale Bedingungen für die DNA-Synthese vorliegen. Die genaueren Ursachen der Fehlpaarungen sind gegenwärtig Gegenstand vieler Diskussionen. Man ist sich zwar einig, daß ein templatgesteuertes Ablesen des H-Substitutionsmusters der heterocyclischen Basen entscheidend für die korrekte Basenpaarung während der DNA-Synthese ist, doch ist noch unklar, welche Art des falschen Ablesens zu einer Fehlpaarung führt. Diskutiert werden das fehlerhafte Ablesen aufgrund einer Nicht-Watson-Crick-Basenpaarbildung und aufgrund einer Änderung des H-Substitutionsmusters, die aber noch zu Watson-Crick-ähnlichen Basenpaaren führt. Die überraschende Entdeckung einer selektiven und quantitativen, durch DNA-Polymerase katalysierten Bildung eines Pyrimidin-Pyridin-Basenpaares (bei Verwendung eines Pyridin-Nucleotidbasen-Analogons) weist darauf hin, daß seltene tautomere Formen im Templat-DNA-Strang zu Watson-Crick-ähnlichen fehlerhaften Basenpaaren führen können, die kaum vom Korrektursystem der Polymerase erkannt werden. Diese Beobachtung zeigt neue Wege für Substitutionsmutationen auf (replikationsabhängige DNA-Punktmutationen) und läßt auf einen neuen Mutagenitätstyp in vivo schließen.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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