Zusammenfassung
□ In raschem Tempo werden immer neue Faktoren identifiziert, die möglicherweise pathogenetisch bedeutsam sind. Zur Charakterisierung der pathogenetischen Relevanz eines Einzelfaktors sind in der Regel spezifische Interventionsstudien in vivo notwendig. Im vorliegenden Artikel wird eine neue Klasse von spezifischen Inhibitoren, die sogenannten Aptamere, vorgestellt. Aptamere (abgeleitet vom lateinischen “aptus”=passend) sind kurze DNA- oder RNA-Oligomere, die über ihre dreidimensionale Struktur hochaffin und sehr spezifisch an Liganden binden und dadurch beispielsweise deren biologische Funktion inhibieren können. Aptamere sind gegen eine Vielzahl verschiedener Moleküle, von Aminosäuren bis zu komplexen Proteinen und selbst Disacchariden, synthetisiert worden. Am Beispiel des „Platelet-Derived Growth Factor” (PDGF) und eines Glomerulonephritis-Modells in der Ratte wird der Effekt eines antagonistischen Aptamers gegen PDGF-B in vivo beschrieben. Solche Untersuchungen werden wesentlich dazu beitragen, die Rolle bestimmter Mediatoren in vivo aufzuklären und neue Therapiestrategien zu entwickeln.
Abstract
□ A rapidly growing number of factors is identified that might contribute to disease. To characterize the pathogenetic relevance of a particular factor, specific intervention studies in vivo appear necessary. The present discussion deals with a new class of inhibitors, i.e. aptamers. Aptamers (derived from the latin word “aptus”= fitting) are short DNA or RNA oligomers which can bind to a given ligand with high affinity and specificity due to their particular three-dimensional structure and which may thereby, for example, antagonize the biological function of the ligand. Aptamers have been generated against a large variety of molecules ranging from amino acids to complex proteins and even disaccharides. Using platelet-derived growth factor (PDGF) and an experimental mesangioproliferative glomerulonephritis as a model, we describe the in vivo effects of an antagonistic aptamer against PDGF-B. Such studies will greatly aid the identification of the biological role of particular mediators and ultimately the design of novel therapeutic strategies.
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Ostendorf, T., Floege, J. Aptamere: ein neuer Ansatz für Interventionsstudien und zur Entwicklung zukünftiger Therapieansätze. Med Klin 94, 219–223 (1999). https://doi.org/10.1007/BF03044858
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DOI: https://doi.org/10.1007/BF03044858