Nature-derived peptides: a growing niche for GPCR ligand discovery

G protein-coupled receptors (GPCRs) represent important drug targets, as they regulate pivotal physiological processes and they have proved to be readily druggable. Natural products have been and continue to be amongst the most valuable sources for drug discovery and development. Peptides from plants, insects or venomous animals are of interest as lead compounds for the development of GPCR ligands, since they cover a chemical space, which differs from that of synthetic small molecules. Peptides, however, face challenges in drug development, some of which can be overcome by studying plant-derived compounds. We argue and will present examples that utilizing circular plant peptides, called cyclotides present an opportunity for GPCR ligand discovery and development [1]-[3].

• References

• 1 Muratspahic E, Freissmuth M, Gruber CW. Nature-derived peptides: a growing niche for GPCR ligand discovery. Trends Pharmacol Sci 2019; 40: 309-326.
• 2 Koehbach J, O’Brien M, Muttenthaler M, Miazzo M, Akcan M, AG Elliott. et al. Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proc Natl Acad Sci USA 2013; 110: 21183-21188.
• 3 Thell K, Hellinger R, Sahin E, Michenthaler P, Gold-Binder M, Haider T. et al. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis. Proc Natl Acad Sci USA 2016; 113: 3960-5.