Continuing challenges in targeting oligomeric GPCR-based drugs

Joaquin Botta; Julia Appelhans; Peter J McCormick

doi:10.1016/bs.pmbts.2019.11.009

Continuing challenges in targeting oligomeric GPCR-based drugs

Prog Mol Biol Transl Sci. 2020:169:213-245. doi: 10.1016/bs.pmbts.2019.11.009. Epub 2020 Jan 3.

Authors

Joaquin Botta¹, Julia Appelhans¹, Peter J McCormick²

Affiliations

¹ Centre for Endocrinology, William Harvey Research Institute, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
² Centre for Endocrinology, William Harvey Research Institute, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. Electronic address: peter.mccormick@outlook.com.

PMID: 31952687
DOI: 10.1016/bs.pmbts.2019.11.009

Abstract

This chapter will focus on the therapeutic potential of oligomeric GPCR structures. We will discuss the history of these complexes and their connection with treatment. We will highlight several examples from the literature of complexes of therapeutic or theranostic opportunity. As part of this we will discuss different mechanisms that oligomers use to modulate their partner that could be taken advantage of from a drug targeting perspective. We will also discuss the challenges and hurdles to targeting such complexes.

Keywords: Bivalent ligands; G protein-coupled oligomers; GPCR cross-talk; GPCR homomers; Heteromers; Interference peptides.

Publication types

Review

MeSH terms

Allosteric Site
Animals
Arrestins / chemistry
Crystallography, X-Ray
Drug Delivery Systems*
Drug Design
Drug Discovery*
Humans
Ligands
Mice
Peptides / chemistry*
Precision Medicine
Protein Multimerization
Protein Transport
Receptors, G-Protein-Coupled / chemistry*
Rhodopsin / chemistry
Signal Transduction

Substances

Arrestins
Ligands
Peptides
Receptors, G-Protein-Coupled
Rhodopsin