Rational Modification of the Biological Profile of GPCR Ligands through Combination with Other Biologically Active Moieties.
In recent years, G protein-coupled receptor (GPCR) ligands have not only been modified by conducting structure-activity relationship studies of leads and known ligands, but several new approaches have emerged in which GPCR ligands were connected or merged with other biologically active molecules. Identical or related ligands were combined to bivalent ones. Orthosteric ligands were combined with allosteric ligands, sometimes leading to dualsteric ones, and also chemical structures were merged to dual-acting or multifunctional compounds. In this article, we want to present some representative examples for these approaches at different GPCRs, showing the versatility of this approach, with a focus on our own work and references to related articles and reviews.
Pharmazeutische und Medizinische Chemie, Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Guozheng
G
Huang
Pharmazeutische und Medizinische Chemie, Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Martin
M
Nimczick
Pharmazeutische und Medizinische Chemie, Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Michael
M
Decker
D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D008024:Ligands; D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled
Bivalent ligand; Drug design; Hybrid molecule; Multifunctional ligand