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Journal of Molecular Modeling

, Volume 15, Issue 6, pp 665–672 | Cite as

Search for inhibitors of AminoAcyl-tRNA synthases by virtual click chemistry

  • Marcin Hoffmann
  • Mieczyslaw Torchala
Original Paper

Abstract

The increase of multidrug-resistant strains of bacteria to known classes of antibiotics present a severe challenge for modern medicine. The most promising strategy to combat pathogenic bacteria is to discover new drug targets. In this regard, aminoacyl-tRNA synthetases are particularly well suited to develop novel drugs that show no cross-resistance to other classical antibiotics. To date various chemical structures that inhibit AA-RS have been identified. In this report we present an interesting approach towards generating of Leu-RS inhibitors by virtual click chemistry. That is we identified key fragments for ligand binding within catalytic pocket of Leu-RS, generated the collection of similar fragments with the use of Ligand.Info, identified the fragments that are most strongly bound in different areas within the catalytic pocket, and finally with the use of virtual click chemistry we generated a set of molecules which are most likely to act as highly potent bacterial Leu-RS inhibitors.

Keywords

Aminoacyl-tRNA synthetases Drug design Molecular docking Virtual click chemistry Virtual screening 

Notes

Acknowledgments

Financial support from European Committee grant no. LSHG-CT-2003-503265 and Polish Ministry for Science is gratefully acknowledged. Authors thank the Foundation for Polish Science for a FOCUS fellowship. Support from Academic Computer Center in Gdańsk (TASK) and Poznan Supercomputing and Networking Center (PCSS) is also gratefully acknowledged. We thank anonymous referees for their remarks.

Supplementary material

894_2008_421_MOESM1_ESM.pdf (267 kb)
ESM (PDF 267 KB)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.BioInfoBank InstitutePoznanPoland
  2. 2.Faculty of ChemistryAdam Mickiewicz UniversityPoznanPoland
  3. 3.Faculty of PhysicsAdam Mickiewicz UniversityPoznanPoland

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