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 RademannEmail author
  • Ronald KühneEmail author
Open Access
Full-Length Paper


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.


Bio informatics Drug design High throughput screening Library design Molecular diversity 



We thank Hans-Dieter Höltje and Victoria Higman for critical reading of the manuscript. The screening data were provided by Jörn Saupe, Samuel Beligny, Svantje Behnken and Susann Matthes. Three institutes, namely the Helmholtz Centre for Infection Research (HZI), the Max Delbrück Centrum (MDC), and the Leibniz Institut für Molekulare Pharmakologie (FMP) co-financed the described screening library, which is now ready to use for supporting screening projects. Extensions to this library are currently made by the MPI in Dortmund, the University of Oslo and the University of Konstanz.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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

Open AccessThis is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License (, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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
    Email author
  • Ronald Kühne
    • 1
    Email author
  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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