Special Issue "Allosteric Modulators"
A special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: closed (15 April 2014)
Dr. Marlene A. Jacobson
Recent advancements in the discovery of allosteric modulators for G protein-coupled receptors (GPCRs) and kinases have revolutionized drug discovery and development. While most currently marketed drugs bind to the orthosteric site for the endogenous ligand, allosteric modulators bind to topographically distinct sites. Orthosteric sites are in general highly conserved across protein superfamilies and identification of highly selective ligands is challenging. Targeting allosteric sites on GPCRs and kinases has emerged as a successful strategy for identification of highly selective ligands with therapeutic utility for the treatment of disease states which previously could not be addressed due to inability to identify subtype selective ligands. In recent years, the discovery of GPCR allosteric modulators as treatments for CNS disorders including schizophrenia, Fragile X and Alzheimer’s disease and allosteric inhibitors for kinases have advanced into clinical development. This special issue invites original research including review articles on the pharmacology, chemical biology and medicinal chemistry of allosteric modulators including assay development and screening technologies, mechanism of action, structural features of binding sites and clinical research and development.
Dr. Marlene A. Jacobson
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access quarterly journal published by MDPI.
- allosteric modulation
- drug discovery
- G protein coupled receptors
- positive allosteric modulator
- negative allosteric modulator
- allosteric inhibitor
- bitopic ligand
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Cross-antagonism as Example of Allosteric Regulation in G-protein-coupled Receptor Heteromers—Cross-antagonism in GPCR Heteromers
Authors: Rafael Franco
Affiliation: 1 Dept. of Biochem. & Mol. Biol. University of Barcelona. Catalonia. Spain
2 Cell and Mol. Neuropharmacol. Laboratory. Nerusociences division. Center for Applied Medical Research. University of Navarra. Spain
Abstract: G-protein-coupled receptors are expressed on the cell surface as heteromers: from heterodimers to hetero-oligomers. In the simplest case an heterodimer is constituted by two different receptors and, importantly, it provides a novel function, which is not merely the addition of the signaling properties of the individual receptors. Although the ultimate consequences of heteromer formation are still under scrutiny and under debate, it has been already demonstrated how dimerization and/or occupancy of one receptor in the dimer affects the binding of agonists to the partner receptor and/or affects the function of the heteromer. According to the current nomenclature these phenomena are considered allosteric. In fact heterodimers are prone to allosteric regulation, and these two mechanisms come by default. In the report the allosteric consequences of heteromerization and of agonist binding to the orthosteric centers in an heteromer are reviewed. Furthermore cross-antagonism, which is a frequently found allosteric modulation in heteromers, is presented and examples are provided and discussed from a physiological and a pharmacological point of view.