Communication

Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors†

  1. Andrew D. Abell Prof.1,3,
  2. Matthew A. Jones Dr.1,
  3. James M. Coxon Prof.1,
  4. James D. Morton Dr.2,
  5. Steven G. Aitken Dr.1,
  6. Stephen B. McNabb Dr.1,
  7. Hannah Y.-Y. Lee Dr.2,
  8. Janna M. Mehrtens Dr.1,
  9. Nathan A. Alexander Dr.1,
  10. Blair G. Stuart1,
  11. Axel T. Neffe Dr.1,4,
  12. Roy Bickerstaffe Prof.2

Article first published online: 14 JAN 2009

DOI: 10.1002/anie.200805014

Issue

Angewandte Chemie International Edition

Angewandte Chemie International Edition

Volume 48, Issue 8, pages 1455–1458, February 9, 2009

Additional Information

How to Cite

Abell, Andrew D., Jones, Matthew A., Coxon, James M., Morton, James D., Aitken, Steven G., McNabb, Stephen B., Lee, Hannah Y.-Y., Mehrtens, Janna M., Alexander, Nathan A., Stuart, Blair G., Neffe, Axel T. and Bickerstaffe, R. (2009), Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors. Angew. Chem. Int. Ed., 48: 1455–1458. doi: 10.1002/anie.200805014

Author Information

  1. 1

    Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch (New Zealand)

  2. 2

    Agriculture and Life Sciences Division, Lincoln University, Post Office Box 84, Canterbury (New Zealand), Fax: (+64) 3-325-3851

  3. 3

    Present address: School of Chemistry & Physics, The University of Adelaide, North Terrace, Adelaide, SA 5005 (Australia), Fax: (+61) 8-8303-4358

  4. 4

    Present address: Institute of Polymer Research, GKSS Research, Centre Geesthacht GmbH, Kantstrasse 55, 14513 Teltow (Germany)

  1. †

    We acknowledge the assistance of Dr. D. Q. McDonald (computational chemistry), Dr. A. Muscroft-Taylor (synthesis), and M. Muir (supply of calpain), and financial support from the New Zealand Public Good Science and Technology Fund, Foundation for Research Science and Technology, the Australian Research Council, and Douglas Pharmaceuticals Limited.

Publication History

  1. Issue published online: 30 JAN 2009
  2. Article first published online: 14 JAN 2009
  3. Manuscript Received: 14 OCT 2008

Funded by

  • New Zealand Public Good Science and Technology Fund, Foundation for Research Science and Technology
  • Australian Research Council
  • Douglas Pharmaceuticals Limited

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Keywords:

  • biological activity;
  • inhibitors;
  • macrocycles;
  • molecular modeling;
  • peptides

Abstract

Thumbnail image of graphical abstract

The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a β-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract treatment. Cbz=carbobenzyloxy.

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