New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development.

5.00
Hdl Handle:
http://hdl.handle.net/10033/620555
Title:
New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development.
Authors:
Klahn, Philipp; Brönstrup, Mark
Abstract:
The development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted. This review negates this impression by showcasing recent achievements in lead finding and optimization of antibiotics that have novel or unexplored chemical structures. Not surprisingly, many of the novel structural templates like teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were discovered from natural sources. Additional compounds were obtained from the screening of synthetic libraries and chemical synthesis, including the gyrase-inhibiting NTBI's and spiropyrimidinetrione, the tarocin and targocil inhibitors of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2.1]octane as novel β-lactamase inhibitors. A motif that is common to most clinically validated antibiotics is that they address hotspots in complex biosynthetic machineries, whose functioning is essential for the bacterial cell. Therefore, an introduction to the biological targets-cell wall synthesis, topoisomerases, the DNA sliding clamp, and membrane-bound electron transport-is given for each of the leads presented here.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development. 2016: Curr. Top. Microbiol. Immunol.
Journal:
Current topics in microbiology and immunology
Issue Date:
5-Oct-2016
URI:
http://hdl.handle.net/10033/620555
DOI:
10.1007/82_2016_501
PubMed ID:
27704270
Type:
Article
ISSN:
0070-217X
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorKlahn, Philippen
dc.contributor.authorBrönstrup, Marken
dc.date.accessioned2016-10-19T08:26:52Z-
dc.date.available2016-10-19T08:26:52Z-
dc.date.issued2016-10-05-
dc.identifier.citationNew Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development. 2016: Curr. Top. Microbiol. Immunol.en
dc.identifier.issn0070-217X-
dc.identifier.pmid27704270-
dc.identifier.doi10.1007/82_2016_501-
dc.identifier.urihttp://hdl.handle.net/10033/620555-
dc.description.abstractThe development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted. This review negates this impression by showcasing recent achievements in lead finding and optimization of antibiotics that have novel or unexplored chemical structures. Not surprisingly, many of the novel structural templates like teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were discovered from natural sources. Additional compounds were obtained from the screening of synthetic libraries and chemical synthesis, including the gyrase-inhibiting NTBI's and spiropyrimidinetrione, the tarocin and targocil inhibitors of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2.1]octane as novel β-lactamase inhibitors. A motif that is common to most clinically validated antibiotics is that they address hotspots in complex biosynthetic machineries, whose functioning is essential for the bacterial cell. Therefore, an introduction to the biological targets-cell wall synthesis, topoisomerases, the DNA sliding clamp, and membrane-bound electron transport-is given for each of the leads presented here.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleNew Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development.
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCurrent topics in microbiology and immunologyen

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