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Hemmstoffe des Folsäure-Stoffwechsels

Inhibitors of folic acid metabolism

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Zusammenfassung

Anders als die Antibiotika-Forschung steht die Erforschung des Folsäure-Stoffwechsels und der Folsäure-Antagonisten ganz in der klassischen aufPaul Ehrlich zurückgehenden Tradition der Chemotherapie. Mit der Aufklärung des Wirkungsmechanismus der Sulfonamide wurde eine wichtige Voraussetzung zum Verständnis der Biosynthese der Folsäure geschaffen. Die Synthese von Inhibitoren der Dihydrofolat-Reduktase orientierte sich einerseits an der Struktur der Dihydrofolsäure selbst, andererseits an der Tatsache, daß diese Substanz für bestimmte Bakterien einen lebenswichtigen Wuchsstoff darstellt. Beide Arbeitsrichtungen führten zu wirksamen und therapeutisch verwendbaren Verbindungen. Die Mechanismen der Selektivität der Folsäure-Antagonisten werden geschildert. Ebenso werden die biochemischen und genetischen Grundlagen der Resistenz gegen Folsäure-Antagonisten beschrieben. Die Erforschung des Folsäure-Stoffwechsels und der Folsäure-Antagonisten liefert ein eindrucksvolles Beispiel für die erfolgreiche Wechselwirkung zwischen einer mechanistisch inspirierten biochemischen und chemischen Methodik einerseits und einer sich an komplexeren biologischen Phänomenen orientierenden empirischen Arbeitsweise andererseits.

Summary

In contrast to antibiotic research, the study of folic acid metabolism and folic acid antagonists is conducted in the classical tradition of chemotherapy established byPaul Ehrlich. The elucidation of the mechanism of action of sulphonamides created an important prerequisite for the understanding of the biosynthesis of folic acid. The synthesis of inhibitors of dihydrofolate-reductase was guided on the one hand by the structure of dihydrofolate itself, and on the other hand by the fact that this substance is essential for the growth of certain bacteria. Both approaches led to the synthesis of compounds which were effective and could be used therapeutically. The mechanism of selectivity of folic acid antagonists is described. A short account of the biochemical and genetic basis of resistance to folic acid antagonists is also given. The study of folic acid metabolism and folic acid antagonists provides a good example of the successful interaction of mechanistically inspired biochemical and chemical methods on the one hand, and an empirical approach characterised by the study of more complex biological phenomena on the other hand.

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  1. Sandoz Forschungsinstitut GmbH, Brunnerstr. 59, A-1235, Wien, Österreich

    J. Drews

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Drews, J. Hemmstoffe des Folsäure-Stoffwechsels. Infection 8 (Suppl 3), S268–S275 (1980). https://doi.org/10.1007/BF01639593

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