Arylamide derivatives as peptidomimetic inhibitors of calmodulin

Hang Yin; Kendra K Frederick; Dahui Liu; A Joshua Wand; William F Degrado

doi:10.1021/ol052478j

Arylamide derivatives as peptidomimetic inhibitors of calmodulin

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

Authors

Hang Yin¹, Kendra K Frederick, Dahui Liu, A Joshua Wand, William F Degrado

Affiliation

¹ Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.

PMID: 16408880
DOI: 10.1021/ol052478j

Abstract

[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

Substances

Amides
Calmodulin
Peptides