Current Drug Discovery Technologies

  • Vladimir P. Torchilin  
    Department of Pharmaceutical Science Center
    for Pharmaceutical Biotechnology and Nanomedicine
    Northeastern University
    Boston, MA 02115


Bivalent Ligands as Specific Pharmacological Tools for G Protein-Coupled Receptor Dimers

Author(s): Isabelle Berque-Bestel, Frank Lezoualc'h and Ralf Jockers

Affiliation: Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Department of Cell Biology, Paris, France.

Keywords: Bivalent ligand, GPCR dimerization, drug design, spacer attachment point, spacer size, spacer chemical structure, heterodimers, GPCR oligomers


G protein-coupled receptors (GPCRs) are major drug targets and are organized in dimeric/oligomeric complexes. These dimers may be composed of identical (homodimer) or different (heterodimer) receptors. GPCR dimerization provides new opportunities for drug design. Different strategies have been developed to specifically target GPCR dimers. Bivalent ligands, which are composed of two functional pharmacophores linked by a spacer, are among the most promising strategies. Due to the constitutive nature of GPCR dimers, bivalent ligands are expected in most cases to bind to and stabilize preexisting dimers rather then to promote ligand-induced dimerization. Most studies on GPCR dimerization were conducted so far in heterologous expression systems. Due the development of heterodimerspecific tools such as bivalent ligands, dimerization has now been confirmed for an increasing number of receptors in native tissues. In this review, we will discuss general considerations for the design and synthesis of bivalent ligands and present the functional in vitro and in vivo properties of reported bivalent ligands.

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Article Details

Page: [312 - 318]
Pages: 7
DOI: 10.2174/157016308786733591