Use of a fluorescent polarization based high throughput assay to identify new calmodulin ligands.
In order to develop a fluorescence polarization (FP) assay for calcium binding proteins, a fluorescent peptides based library of 1328 compounds has been synthesized. The use of this library has been validated by setting up a FP-high-throughput screening (FP-HTS) assay for calmodulin using the synthetic gene product (synCaM). With this assay, a set of 880 FDA approved compounds was screened. Besides the promazine class, we discovered two new classes of compounds that interact with calmodulin in a calcium dependent manner. One class has compounds with anti-histaminic/spasmolytic activities, and the other one are detergents with antibacterial activities.
Dagher
Rania
R
UMR 7175- LC1, Institut Gilbert Laustriat, Département de Pharmacochimie de la Communication Cellulaire, France.
Pigault
Claire
C
Bonnet
Dominique
D
Boeglin
Damien
D
Pourbaix
Christelle
C
Kilhoffer
Marie-Claude
MC
Villa
Pascal
P
Wermuth
Camille G
CG
Hibert
Marcel
M
Haiech
Jacques
J
D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D002147:Calmodulin / Q000737:chemistry* / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005454:Fluorescence Polarization / Q000379:methods*; D008024:Ligands; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D008024:Ligands; D019151:Peptide Library; D010455:Peptides