Arylamide derivatives as peptidomimetic inhibitors of calmodulin.
[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.
Yin
Hang
H
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Frederick
Kendra K
KK
Liu
Dahui
D
Wand
A Joshua
AJ
Degrado
William F
WF
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000595:Amino Acid Sequence; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D005454:Fluorescence Polarization / Q000379:methods; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation
D000577:Amides; D002147:Calmodulin; D010455:Peptides