Design of multivalent ligand targeting G-protein-coupled receptors.

More and more evidences are still accumulating rapidly on the G-protein-coupled-receptors (GPCRs) dimerization/oligomerization. Such common feature of GPCRs has called extensive attention to both pharmacologists and medicinal chemists for illustration of the pharmacological functions and therapeutic utilities of such receptor complex. Although there is still no clear explanation for the receptor dimerization/oligomerization, a large number of multivalent ligands (MLs) have been designed to target the receptor-dimers/oligomers. Such MLs have gained much acceptance in exploring the receptor complex of dopaminergic, adrenergic, serotoninergic, and opioidic receptor systems, due to the relatively broader experience in recognizing the receptor-dimerization. More and more MLs have also been designed to face GPCR-related very complex neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD) and schizophrenia, which are not effectively treated by traditional highly selective drugs. Herein, some of the most recent developments in this field, as well as some typical examples of MLs, are highlighted, with a particular focus on GPCRs.