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Using Ligand-Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo-Like Kinase 1†

  1. Yaw Sing Tan1,‡,
  2. Dr. Paweł Śledź1,2,‡,
  3. Dr. Steffen Lang1,
  4. Christopher J. Stubbs1,
  5. Dr. David R. Spring1,
  6. Prof. Chris Abell1,*,
  7. Dr. Robert B. Best1,*

Article first published online: 7 SEP 2012

DOI: 10.1002/ange.201205676

Issue

Angewandte Chemie

Angewandte Chemie

Volume 124, Issue 40, pages 10225–10228, October 1, 2012

Additional Information

How to Cite

Tan, Y. S., Śledź, P., Lang, S., Stubbs, C. J., Spring, D. R., Abell, C. and Best, R. B. (2012), Using Ligand-Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo-Like Kinase 1 . Angew. Chem., 124: 10225–10228. doi: 10.1002/ange.201205676

Author Information

  1. 1

    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK)

  2. 2

    Present address: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried (Germany)

  1. ‡

    These authors contributed equally to this work.

*Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK)

  1. †

    We are grateful for funding from the Agency for Science, Technology and Research (Y.S.T.), the Wellcome Trust, the Gates Cambridge Trust, St. Edmund’s College (P.Ś.) and DAAD (S.L.). R.B.B. is supported by a Royal Society University Research Fellowship. We thank Dr. Marko Hyvönen for assistance with the structural biology, Dr. Chandra Verma for helpful discussions.

  2. ‡

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 26 SEP 2012
  2. Article first published online: 7 SEP 2012
  3. Manuscript Received: 17 JUL 2012

Funded by

  • Funded Access
  • Agency for Science, Technology and Research
  • Wellcome Trust
  • Gates Cambridge Trust
  • St. Edmund’s College
  • DAAD

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Keywords:

  • Molekulare Erkennung;
  • Moleküldynamik;
  • Proteindynamik;
  • Protein-Protein-Wechselwirkungen;
  • Wirkstoffentwicklung
Thumbnail image of graphical abstract

Ein Verfahren mit expliziter Ligandenkartierung war geeignet, um eine unerkannt gebliebene hydrophobe Tasche in der Polo-like Kinase 1 (Plk1) zu entdecken. Ein neuartiger Ligandenbindungsmodus konnte vorhergesagt und für den Entwurf eines neuen Liganden mit hoher Affinität für Plk1 genutzt werden. Eine Röntgenstrukturanalyse bestätigt eine spezifische Bindung des Liganden in der vorgesehenen Tasche.

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