Arylamide derivatives as peptidomimetic inhibitors of calmodulin

Org Lett. 2006 Jan 19;8(2):223-5. doi: 10.1021/ol052478j.


[structure: see text] Many peptides bind to calmodulin (CaM) in a helical conformation. Here we describe a group of synthetic inhibitors of CaM based on an arylamide scaffold that is intended to mimic smMLCK, a CaM-binding helical peptide. Compound 1 showed a K(i) value of 7.10 +/- 1.48 nM in a fluorescence polarization assay that monitors the strong association of CaM and its peptide ligand mastoparan X. ((1)H,(15)N)-HSQC NMR spectroscopy experiments suggested that 1 binds to CaM in an analogous fashion to that of smMLCK.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Amino Acid Sequence
  • Calmodulin / antagonists & inhibitors*
  • Fluorescence Polarization / methods
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Protein Conformation


  • Amides
  • Calmodulin
  • Peptides