Rational Modification of the Biological Profile of GPCR Ligands through Combination with Other Biologically Active Moieties

Arch Pharm (Weinheim). 2015 Aug;348(8):531-40. doi: 10.1002/ardp.201500079. Epub 2015 May 4.

Abstract

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.

Keywords: Bivalent ligand; Drug design; Hybrid molecule; Multifunctional ligand.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Drug Design*
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • Pharmaceutical Preparations* / chemistry
  • Pharmaceutical Preparations* / metabolism
  • Protein Binding
  • Protein Conformation
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Ligands
  • Pharmaceutical Preparations
  • Receptors, G-Protein-Coupled