3 April 2020
New research from Monash Institute of Pharmaceutical Sciences (MIPS), in collaboration with the Max Planck Institute, Mayo Clinic, University of Auckland, University of Essex and University of Tokyo, has uncovered new structures of protein receptors, a step forward for the design of new drugs to treat heart attacks and infertility.
The research, published in ACS Pharmacology and Translational Science and co-led by Associate Professor Denise Wootten and Professor Patrick Sexton from MIPS’ Drug Discovery Biology, has tapped into the peptide adrenomedullin (AM) receptor structures with their research team.
In a major breakthrough, the researchers have shone a light on AM receptor subtype structures by using cryo-electron microscopy (cryo-EM) to uncover previously unseen fine molecular details of how different AM receptors function. These findings have potential to initiate rational, structure-assisted design of new drugs.
The peptide adrenomedullin (AM) plays a crucial role in healthy development of both lymph and blood vessels. The actions of AM (and related peptides) is via AM receptors (AM1R and AM2R) and these receptors are targets for potential new drug treatments of diseases including infertility, hypertension, heart attack, and inflammatory bowel disease.
Co-lead on the project, Associate Professor Denise Wootten, says that the findings open up new approaches to drug development.
“These receptors have a higher level of complexity than many other related receptors. We’ve managed to unlock the distinctions between AM receptor subtypes which is a fundamental first step for new drug design,” A/Prof Wootten said.
Professor Patrick Sexton adds that cryo-EM is a key player into understanding receptor structure.
“Cryo-EM enables us to use the physiological form of the receptor to see molecular details of the receptors, but importantly using this method we can now observe the motions of these proteins” Professor Sexton said. “This was a key factor in understanding how AM receptors work”
“This study is a major leap forward in researchers being able to use structures for future drug development. Understanding how these receptors work can really pave the way for us to develop new medicines for crucial health burdens.”
Full details of the work can be found at: https://doi.org/10.1021/acsptsci.9b00080
Read the full media release here.