title: Protein-Protein Interactions as New Targets for Ion Channel Drug Discovery.
abstract: Protein-protein interactions (PPI) are key molecular elements that provide the basis of signaling in virtually all cellular processes. The precision and specificity of these molecular interactions have ignited a strong interest in pursuing PPI surfaces as new targets for drug discovery, especially against ion channels in the central nervous system (CNS) where selectivity and specificity are vital for developing drugs with limited side effects. Ion channels are large transmembrane domain proteins assembled with multiple regulatory proteins binding to the intracellular portion of channels. These macromolecular complexes are difficult to isolate, purify and reconstitute, posing a significant barrier in targeting these PPI for drug discovery purposes. Here, we will provide a short overview of salient features of PPI and discuss successful studies focusing on protein-channel interactions that could inspire new drug discovery campaigns targeting ion channel complexes.
authors.affiliation: Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555, USA ; Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Svetla
authors.initials: S
authors.lastname: Stoilova-McPhie
authors.affiliation: Department Pharmacology & Toxicology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Syed
authors.initials: S
authors.lastname: Ali
authors.affiliation: Department Pharmacology & Toxicology, The University of Texas Medical Branch, Galveston, TX 77555, USA ; Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77555, USA ; Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Laezza
keywords: Cell proliferation; Drug discovery; Ion channels; Protein– Interaction; Signal transduction