2. Academic Validation
  3. Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases and cancer metastasis

Synthesis and biological evaluation of analogues of the potent ADAM8 inhibitor cyclo(RLsKDK) for the treatment of inflammatory diseases and cancer metastasis

  • Bioorg Med Chem. 2016 Sep 15;24(18):4032-4037. doi: 10.1016/j.bmc.2016.06.042.
Victor Yim 1,  Anaïs F M Noisier 1,  Kuo-Yuan Hung 1,  Jörg W Bartsch 2,  Uwe Schlomann 2,  Margaret A Brimble 3
Affiliations

Affiliations

  • 1 School of Biological Sciences and The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 3a Symonds St, Auckland Central 1010, New Zealand.
  • 2 Department of Neurosurgery, Marburg University, University Hospital, Baldingerstr., 35053 Marburg, Germany.
  • 3 School of Biological Sciences and The Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, 3a Symonds St, Auckland Central 1010, New Zealand; School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1010, New Zealand. Electronic address: m.brimble@auckland.ac.nz.
PMID: 27407033 DOI: 10.1016/j.bmc.2016.06.042
Abstract

The metalloproteinase ADAM8 serves as a pivotal catalyst in the development of inflammatory diseases and Cancer metastasis. The cyclic peptide cyclo(RLsKDK) has been shown to inhibit the enzymatic activity of ADAM8 with high specificity and potency. Herein we report a structure-activity relationship (SAR) study of cyclo(RLsKDK) that involves the synthesis and biological evaluation of the lead compound and structural analogues thereof. This study provides insight into the ligand-receptor interactions that govern the binding of cyclo(RLsKDK) to the ADAM8 disintegrin domain and represents a stepping stone for the development of new treatments for inflammatory diseases and Cancer metastasis.

Keywords

ADAM8 inhibitors; Cancer metastasis; Cyclic peptides; Peptidomimetics; SAR study.

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