UNRAVELLING THE BINDING AND ACTIVATION MECHANISM OF A COMPLEX G PROTEIN-COUPLED RECEPTOR
Grant number: 1100676 | Funding period: 2016 - 2019
The peptide hormone relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin with its cell surface receptor and the mechanisms by which the receptor functions. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin for the treatment of heart failure
Related publications (9)
Conformational Changes in Tyrosine 11 of Neurotensin Are Required to Activate the Neurotensin Receptor 1
Fabian Bumbak, Trayder Thomas, Billy J Noonan-Williams, Tasneem M Vaid, Fei Yan, Alice R Whitehead, Shoni Bruell, Martina Kocan, Xuan Tan, Margaret A Johnson, Ross AD Bathgate, David K Chalmers, Paul R Gooley, Daniel J Scott
Cell-cell communication via endogenous peptides and their receptors is vital for controlling all aspects of human physiology and m..
The anti-fibrotic actions of relaxin are mediated through AT(2)R-associated protein phosphatases via RXFP1-AT(2)R functional crosstalk in human cardiac myofibroblasts
Chao Wang, Anita A Pinar, Robert E Widdop, Mohammed A Hossain, Ross AD Bathgate, Kate M Denton, Barbara K Kemp-Harper, Chrishan S Samuel
Fibrosis is a hallmark of several cardiovascular diseases. The relaxin family peptide receptor 1 (RXFP1) agonist, relaxin, has rap..
Familial bilateral cryptorchidism is caused by recessive variants in RXFP2
Katie Ayers, Rakesh Kumar, Gorjana Robevska, Shoni Bruell, Katrina Bell, Muneer A Malik, Ross A Bathgate, Andrew Sinclair
BACKGROUND: Cryptorchidism or failure of testicular descent is the most common genitourinary birth defect in males. While both the..
Using the novel HiBiT tag to label cell surface relaxin receptors for BRET proximity analysis
Bradley L Hoare, Martina Kocan, Shoni Bruell, Daniel J Scott, Ross AD Bathgate
Relaxin family peptide 1 (RXFP1) is the receptor for relaxin a peptide hormone with important therapeutic potential. Like many G p..
Multi-Component Mechanism of H2 Relaxin Binding to RXFP1 through NanoBRET Kinetic Analysis
Bradley L Hoare, Shoni Bruell, Ashish Sethi, Paul R Gooley, Michael J Lew, Mohammed A Hossain, Asuka Inoue, Daniel J Scott, Ross AD Bathgate
The peptide hormone H2 relaxin has demonstrated promise as a therapeutic, but mimetic development has been hindered by the poorly ..
Real-time examination of cAMP activity at relaxin family peptide receptors using a BRET-based biosensor
Adam L Valkovic, Miranda B Leckey, Alice R Whitehead, Mohammed A Hossain, Asuka Inoue, Martina Kocan, Ross AD Bathgate
Relaxin family peptide (RXFPs) 1-4 receptors modulate the activity of cyclic adenosine monophosphate (cAMP) to produce a range of ..
Distinct activation modes of the Relaxin Family Peptide Receptor 2 in response to insulin-like peptide 3 and relaxin
Shoni Bruell, Ashish Sethi, Nicholas Smith, Daniel J Scott, Mohammed Akhter Hossain, Qing-Ping Wu, Zhan-Yun Guo, Emma J Petrie, Paul R Gooley, Ross AD Bathgate
Relaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It is structurally related to the..