Ribosomal Alterations Contribute to Bacterial Resistance against the Dipeptide Antibiotic TAN 1057

Limburg, E.; Gahlmann, Reinhold; Kroll, Hein‐Peter; Beyer, D.

doi:10.1128/aac.48.2.619-622.2004

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…Competition experiments with other antibiotics, inhibiting peptidyl transferase, revealed a unique binding site for 127 / 128 321. Consequently, S. aureus subtypes selected for 127 / 128 resistance did not show cross‐resistance to a panel of known inhibitors of bacterial translation 322. Natural 127 / 128 showed a comparable, nonspecific inhibitory activity in cell‐free translation assays derived from prokaryotes and eukaryotes,321 which could be the reason for the natural product's high acute toxicity in mice (LD 50 50 mg kg −1 i.v.)…”

Section: Tetrahydropyrimidinone Antibioticsmentioning

confidence: 96%

Oligothiophene Isothiocyanates as Fluorescent Markers

Barbarella

2002

Chem. Eur. J.

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To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti‐infectives. Surprisingly, numerous “old” classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the “old fashioned” natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target‐finding tools from biology (reversed genomics) is one option for their revival.

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Section: Tetrahydropyrimidinone Antibioticsmentioning

confidence: 96%

Oligothiophene Isothiocyanates as Fluorescent Markers

Barbarella

2002

Chem. Eur. J.

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“…[321] Entsprechend konnte für TAN-1057-resistente S.-aureus-Isolate keine Kreuzresistenz zu anderen Inhibitoren der bakteriellen Translation nachgewiesen werden. [322] Die Naturstoffe 127/128 wiesen in zellfreien prokaryotischen und eukaryotischen Translationsassays eine vergleichbare, unspezifische Inhibitionswirkung auf, [321] [323][324][325] der Diastereomerenmischung TAN-1057A/B (127/128) und eine stereoselektive Synthese [326] des Diastereomers 127 erfolgreich abgeschlossen.…”

Section: Tetrahydropyrimidinon-antibiotikaunclassified

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

et al. 2006

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Zur Entwicklung von Medikamenten müssen die Strukturvorlagen aus der Natur oft durch Semisynthese oder Totalsynthese verbessert werden (chemische Post‐Evolution). Der Weg vom Naturstoff zum Arzneimittel ist mühsam aber lohnenswert. Die grundlegenden Typen der chemischen Naturstoffmodifikation – Dekoration, Substitution und Abbau – werden hier besprochen, und das biologische, chemische und sozioökonomische Umfeld antibakterieller Forschung wird betrachtet. Naturstoffe waren und bleiben die ergiebigste Leitstrukturquelle für vermarktete Antiinfektiva, und obwohl viele lange bekannte Klassen nie grundlegend erforscht worden sind, erlahmen die industrielle wie die akademische Forschung auf diesem Gebiet – die “altmodischen” Naturstoffe scheinen nicht mehr ins Bild der modernen Wirkstoff‐Forschung zu passen, ihre Handhabung ist aufwändig und erfordert oft nichtstandardisierte Prozesse und längere Bearbeitungszeiten. Eine Neubetrachtung von Naturstoffen mit Methoden der modernen Chemie und Biologie (Reversed Genomics) könnte ihre Renaissance in der Arzneimittelforschung einleiten.

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“…Several other ribosome‐targeting antibiotics are currently at different stages of development and characterization. These include pleuromutilins (Schlunzen et al ., 2004), TAN‐1057 (Limburg et al ., 2004), evernimicin (Belova et al ., 2001) and several others. An example of structure‐based drug design potential is represented by a series of compounds being developed by Rib‐X, a start‐up biotechnology company that uses ribosome crystallography and computational modelling as the main guides for development of new drugs (Ippolito et al ., 2005).…”

Section: New Drugsmentioning

confidence: 99%

Antibiotics and the ribosome

Tenson

Mankin

2006

Molecular Microbiology

142

112

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SummaryThe ribosome is one of the main antibiotic targets in the cell. Recent years brought important insights into the mode of interaction of antibiotics with the ribosome and mechanisms of antibiotic action. Ribosome crystallography provided a detailed view of the interactions between antibiotics and rRNA. Advances in biochemical techniques let us better understand how the binding of small organic molecules can interfere with functions of an enzyme four orders of magnitude larger than the inhibitor. These and other achievements paved the way for the development of new ribosome-targeting antibiotics, some of which have already entered medical practice. The recent progress, problems and new directions of research of ribosome-targeting antibiotics are discussed in this review.

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Ribosomal Alterations Contribute to Bacterial Resistance against the Dipeptide Antibiotic TAN 1057

Cited by 12 publications

References 24 publications

Oligothiophene Isothiocyanates as Fluorescent Markers

Oligothiophene Isothiocyanates as Fluorescent Markers

Antibakterielle Naturstoffe in der medizinischen Chemie – Exodus oder Renaissance?

Antibiotics and the ribosome

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