Peptide Design Strategies for G-Protein Coupled Receptors (GPCR)

Peptides act as primary source of intercellular communication in many diverse biological systems by interacting with their corresponding receptors. A large subset of these receptors couple with G-proteins to produce a signal transduction cascade of cellular actions, hence called G-protein coupled receptors (GPCRs). Generally, the event of receptor activation may be divided into at least four steps: ligand binding and signal generation, ligand induced GPCR structural changes, signal transduction, and signal transfer to cytoplasmic signal molecules. Peptide hormones play an essential role in most physiological systems. Structure and activity studies of peptide hormones are an important tool to analyze ligand-receptor interaction; other methods are photoaffinity labeling, site-directed mutagenesis, the construction of receptor chimeras and molecular modeling. Some of the methods are discusses by taking examples from peptidergic GPCR family, primarily the melanocortin system.