Structure-Activity Relationship Studies: Methods and Ligand Design for G-Protein Coupled Peptide Receptors

The exchange of information between cells represents an important regulatory mechanism for cellular activities. Such regulation processes mainly occur by hydrophilic compounds, unable to penetrate the cell membrane. Accordingly such signals have to be transmitted into the cell that is performed by transmembrane receptors. The widespread group of G-protein coupled receptors plays a decisive role in extracellular signal recognition and transition into cellular response. The importance of this interaction is evidently shown by the severe diseases that correlate with dysfunction of the interaction between ligand and G-protein coupled receptor. The development of drugs against these diseases needs the comprehension of signal recognition and transition as well as the understanding of intracellular signal pathways. In this review, we describe concepts and methods to identify the structure-activity relationships of G-protein coupled peptide receptors and their successful application. Furthermore we provide an insight into peptide based drug design. Examples are taken from the field of CGRP, orexin and growth hormone secretagogue receptor ligands. Keywords: Signal Transduction, second messenger, growth hormone secretagogue receptor (GHS-R), Ca binding proteins, receptor conformation