Article
Biochemistry & Molecular Biology
Adam L. Valkovic, Martina Kocan, Brad Hoare, Sarah Marshall, Daniel J. Scott, Ross A. D. Bathgate
Summary: This article introduces a new BRET-based cGMP sensor called CYGYEL, which enables efficient and rapid detection of cGMP activity in plate-based assays and successfully detects cGMP signals in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Mengjie Liu, Barbara F. White, Praveen Praveen, Wenyi Li, Feng Lin, Hongkang Wu, Rong Li, Carlie Delaine, Briony E. Forbes, John D. Wade, Mohammed Akhter Hossain
Summary: The study reported an efficient synthesis method for a novel disulfide dimer of human insulin, which has a similar structure to native insulin and comparable affinity to both the insulin receptor and insulin-like growth factor-1 receptor. In insulin tolerance tests, the dimeric insulin showed equipotency to Actrapid and a sustained duration of action surpassing that of Actrapid and Glargine.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ashish Sethi, Shoni Bruell, Tim Ryan, Fei Yan, Mohammad Hossein Tanipour, Yee-Foong Mok, Chris Draper-Joyce, Yogesh Khandokar, Riley D. Metcalfe, Michael D. W. Griffin, Daniel J. Scott, Mohammad Akhter Hossain, Emma J. Petrie, Ross A. D. Bathgate, Paul R. Gooley
Summary: The conserved motif in the C-terminal of the LDLa module is critical for receptor activity in RXFP1 and RXFP2, with different structures adopted in these two receptors suggesting distinct activation mechanisms. This difference in activation mechanisms could be beneficial for drug development targeting these receptors.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Biographical-Item
Biochemistry & Molecular Biology
John D. Wade, John H. Jones
Summary: Robert Charles Sheppard, also known as Bob Sheppard among friends, was a pioneering figure in solid phase peptide synthesis, making significant contributions to the art of peptide synthesis in Europe since Emil Fischer.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Annunziata D'Ercole, Silvia Nistri, Lorenzo Pacini, Alfonso Carotenuto, Federica Santoro, Anna Maria Papini, Ross A. D. Bathgate, Daniele Bani, Paolo Rovero
Summary: This study synthesized and tested a set of low molecular weight peptides in order to obtain RLX analogues with improved pharmacokinetic features. However, none of these peptides showed sufficient affinity to the specific RLX receptor RXFP1 or RLX-like biological effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yan Chen, Qingtong Zhou, Jiang Wang, Youwei Xu, Yun Wang, Jiahui Yan, Yibing Wang, Qi Zhu, Fenghui Zhao, Chenghao Li, Chuan-Wei Chen, Xiaoqing Cai, Ross A. . D. Bathgate, Chun Shen, H. Eric Xu, Dehua Yang, Hong Liu, Ming-Wei Wang
Summary: The authors reveal the ligand-binding modes and key determinants of peptidomimetic agonism and subtype selectivity through cryo-EM structures. This study provides insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, and expands the knowledge of signaling mechanisms in the insulin superfamily.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Stephane Illiano, Bruno Poirier, Claire Minoletti, Olivier Pasquier, Laurence Riva, Xavier Chenede, Isabelle Menguy, Michel Guillotel, Philippe Prigent, Stephane Le Claire, Florence Gillot, Gilbert Thill, Francois Lo Presti, Alain Corbier, Jean-Christophe Le Bail, Patrick Grailhe, Edith Monteagudo, Raffaele Ingenito, Elisabetta Bianchi, Christophe Philippo, Olivier Duclos, Sergio Mallart, Ross Bathgate, Philip Janiak
Summary: A new long-lasting RXFP1 agonist, SA10SC-RLX, has been developed and shown to mimic the activity of relaxin. It can be administered subcutaneously and has potential for treating chronic fibrotic and cardiovascular diseases.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Fabian Bumbak, Miquel Pons, Asuka Inoue, Juan Carlos Paniagua, Fei Yan, Hongwei Wu, Scott A. Robson, Ross A. D. Bathgate, Daniel J. Scott, Paul R. Gooley, Joshua J. Ziarek
Summary: Nuclear magnetic resonance (NMR) studies have shown that fast methyl sidechain dynamics can provide information about entropically-driven allostery. This study focuses on the fast dynamics of a thermostabilized G protein-coupled receptor (GPCR), neurotensin receptor 1 (NTS1), using 13C epsilon-methionine chemical shift-based global order parameters. The results indicate the presence of substates with different lifetimes in the NTS1 solution ensemble, and the rapid fluctuations of individual methionine residues are correlated with ligand pharmacology, suggesting a role for sub-microsecond dynamics and conformational entropy in GPCR ligand discrimination.
Article
Medicine, Research & Experimental
Fariha Alam, Tracey A. Gaspari, Barbara K. Kemp-Harper, Edward Low, Aaron Aw, Dorota Ferens, Iresha Spizzo, Ann-Maree Jefferis, Praveen Praveen, Robert E. Widdop, Ross A. D. Bathgate, Mohammed Akhter Hossain, Chrishan S. Samuel
Summary: This study found that B7-33 can retain the cardioprotective effects of RLX and has a better therapeutic effect compared to the ACE inhibitor perindopril. Therefore, B7-33 could be considered as a cost-effective cardioprotective therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Obstetrics & Gynecology
Ann-Kristin Dicke, Jakob Albrethsen, Bradley L. Hoare, Margot J. Wyrwoll, Alexander S. Busch, Daniela Fietz, Adrian Pilatz, Clara Buehlmann, Anders Juul, Sabine Kliesch, Joerg Gromoll, Ross A. D. Bathgate, Frank Tuettelmann, Birgit Stallmeyer
Summary: This study reveals that bi-allelic loss-of-function variants in the INSL3 and RXFP2 genes are associated with bilateral cryptorchidism and male infertility, while heterozygous variant carriers are unaffected phenotypically. These findings have diagnostic value for patients with familial/bilateral cryptorchidism and shed light on the importance of INSL3 and RXFP2 in testicular descent and fertility.
HUMAN REPRODUCTION
(2023)
Article
Biochemistry & Molecular Biology
Praveen Praveen, Chao Wang, Thomas N. G. Handley, Hongkang Wu, Chrishan S. S. Samuel, Ross A. D. Bathgate, Mohammed Akhter Hossain
Summary: Human relaxin-2 (H2 relaxin) has therapeutic importance due to its anti-fibrotic, vasodilatory, and cardioprotective effects. Relaxin family peptide receptor 1 (RXFP1), the receptor for relaxin, is a potential target for treating fibrosis and related disorders. A single-chain agonist, B7-33 peptide, has been developed based on the B-chain of H2 relaxin but has a short circulation time in vitro.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shubo Jin, Erin. J. J. Campbell, Chi Kin Ip, Sharon Layfield, Ross A. D. Bathgate, Herbert Herzog, Andrew. J. J. Lawrence
Summary: The nucleus accumbens shell is an important part of the reward circuit, responsible for encoding reward-associated environments. This study identified the ventral subiculum as the brain region with the highest glutamatergic input to the shell. By analyzing the molecular characteristics of different glutamatergic projections from the ventral subiculum to the nucleus accumbens shell, the study revealed differential gene enrichment and highlighted potential differences in neuronal projections.
NEUROCHEMICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Mohammed Akhter Hossain, Praveen Praveen, Nurhayati Ahmad Noorzi, Hongkang Wu, Ian P. Harrison, Thomas Handley, Stavros Selemidis, Chrishan S. Samuel, Ross A. D. Bathgate
Summary: H2 relaxin is a peptide hormone that acts through the RXFP1 receptor and has important biological functions. Overexpression of H2 relaxin and RXFP1 in prostate cancer suggests their potential as targets for inhibiting tumor growth. In this study, a novel high-affinity RXFP1 antagonist, H2 B-R13HR, was developed and shown to inhibit relaxin-mediated tumor growth in a mouse model. This compound provides insights into relaxin actions through RXFP1 and may have therapeutic potential for prostate cancer.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Rong Li, Thomas N. G. Handley, Wenyi Li, Neil M. O'Brien-Simpson, Mohammed Akhter Hossain, John D. Wade
Summary: Antimicrobial resistance is increasing and causing 700,000 deaths worldwide in 2020. Antimicrobial peptides are effective against drug-resistant pathogens and have a lower risk of developing resistance. Dimerisation of antimicrobial peptides through disulfide bonds can enhance antimicrobial activity and reduce toxicity.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Thomas N. G. Handley, Praveen Praveen, Julien Tailhades, Hongkang Wu, Ross A. D. Bathgate, Mohammed Akhter Hossain
Summary: H2 relaxin is a peptide hormone with vasodilatory and anti-fibrotic effects. Researchers have developed B7-33, a derived peptide from H2 relaxin, which showed equivalent potency and anti-fibrotic effects in fibroblasts. B7-33 also reversed organ fibrosis in pre-clinical animal studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
