Title:Heterotrimeric G Protein α-Subunits - Structures, Peptide-Derived Inhibitors,
and Mechanisms
Volume: 29
Issue: 42
Author(s): Jan H. Voss and Christa E. Müller*
Affiliation:
- PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of
Bonn, An der Immenburg 4, D-53121 Bonn, Germany
Keywords:
Cyclo(depsi)peptide, FR900359, heterotrimeric G protein, Gα protein, G protein-coupled receptor, peptide, YM-254890, inhibitor.
Abstract: G protein-coupled receptors are the largest protein family in the human body
and represent the most important class of drug targets. They receive extracellular signals
and transduce them into the cytosol. The guanine nucleotide-binding Gα proteins represent
the main relays by which GPCRs induce intracellular effects. More than 800 different
GPCRs interact with 16 Gα proteins belonging to 4 families, Gαi, Gαs, Gαq, and
Gα12/13. The direct inhibition of Gα protein subunits rather than the modulation of GPCR
subtypes has been proposed as a novel strategy for the treatment of complex diseases, including
inflammation and cancer. This mini-review presents an introduction to G protein
structure and function and describes achievements in the development of peptidic and
peptide-derived Gα protein inhibitors. They have become indispensable pharmacological
tools, and some of them exhibit significant potential as future drugs.