Molecular Diversity

, Volume 14, Issue 2, pp 401–408 | Cite as

Design of chemical libraries with potentially bioactive molecules applying a maximum common substructure concept

  • Michael Lisurek
  • Bernd Rupp
  • Jörg Wichard
  • Martin Neuenschwander
  • Jens Peter von Kries
  • Ronald Frank
  • Jörg Rademann
  • Ronald Kühne
Open Access
Full-Length Paper

Abstract

Success in small molecule screening relies heavily on the preselection of compounds. Here, we present a strategy for the enrichment of chemical libraries with potentially bioactive compounds integrating the collected knowledge of medicinal chemistry. Employing a genetic algorithm, substructures typically occurring in bioactive compounds were identified using the World Drug Index. Availability of compounds containing the selected substructures was analysed in vendor libraries, and the substructure-specific sublibraries were assembled. Compounds containing reactive, undesired functional groups were omitted. Using a diversity filter for both physico-chemical properties and the substructure composition, the compounds of all the sublibraries were ranked. Accordingly, a screening collection of 16,671 compounds was selected. Diversity and chemical space coverage of the collection indicate that it is highly diverse and well-placed in the chemical space spanned by bioactive compounds. Furthermore, secondary assay-validated hits presented in this study show the practical relevance of our library design strategy.

Keywords

Bio informatics Drug design High throughput screening Library design Molecular diversity 

Supplementary material

11030_2009_9187_MOESM1_ESM.doc (422 kb)
DOC 1 (DOC 422 KB)

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Copyright information

© The Author(s) 2009

Authors and Affiliations

  • Michael Lisurek
    • 1
  • Bernd Rupp
    • 1
  • Jörg Wichard
    • 1
  • Martin Neuenschwander
    • 1
  • Jens Peter von Kries
    • 1
  • Ronald Frank
    • 2
  • Jörg Rademann
    • 1
    • 3
  • Ronald Kühne
    • 1
  1. 1.FMP Leibniz Institut für Molekulare PharmakologieBerlinGermany
  2. 2.Department of Chemical BiologyHZI Helmholz Centre for Infection ResearchBraunschweigGermany
  3. 3.Institut für Chemie und Biochemie, Freie Universität BerlinBerlinGermany

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