Structure-function relationship of human relaxins.
Grant number: 508995 | Funding period: 2008 - 2010
Relaxin is a peptide that is involved in the regulation of the birth process. It has considerable promise as an anti-fibrotic agent. Recently, another relaxin-like peptide, relaxin-3, was identified and shown to be brain-specific. It modulates the stress response and appetite. Both relaxins act upon different receptors to elicit their biological effects. To exploit their clinical potential, we will determine how these peptides selectively bind and ativate their individual receptors.
Related publications (26)
Development of a Single-Chain Peptide Agonist of the Relaxin-3 Receptor Using Hydrocarbon Stapling
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Structure-activity studies of the insulin superfamily member, relaxin-3, have shown that its G protein-coupled receptor (RXFP3) bi..
Native Chemical Ligation to Minimize Aspartimide Formation during Chemical Synthesis of Small LDLa Protein
Julien Tailhades, Ashish Sethi, Emma J Petrie, Paul R Gooley, Ross A Bathgate, John D Wade, Mohammed A Hossain
The inhibition of the G protein-coupled receptor, relaxin family peptide receptor 1 (RXFP1), by a small LDLa protein may be a pote..
Synthetic Covalently Linked Dimeric Form of H2 Relaxin Retains Native RXFP1 Activity and Has Improved In Vitro Serum Stability
Vinojini B Nair, Ross AD Bathgate, Frances Separovic, Chrishan S Samuel, Mohammed Akhter Hossain, John D Wade
Human (H2) relaxin is a two-chain peptide member of the insulin superfamily and possesses potent pleiotropic roles including regul..
Central injection of relaxin-3 receptor (RXFP3) antagonist peptides reduces motivated food seeking and consumption in C57BL/6J mice
Craig M Smith, Berenice E Chua, Cary Zhang, Andrew W Walker, Mouna Haidar, David Hawkes, Fazel Shabanpoor, Mohammad Akhter Hossain, John D Wade, K Johan Rosengren, Andrew L Gundlach
Behavioural arousal in mammals is regulated by various interacting central monoamine- and peptide-neurotransmitter/receptor system..
Minimum Active Structure of Insulin-like Peptide 5
Alessia Begi, Ross AD Bathgate, Martina Kocan, Nitin Patil, Suode Zhang, Geoffrey W Tregear, John D Wade, Mohammed Akhter Hossain
Insulin-like peptide 5 (INSL5) is a complex two-chain peptide hormone constrained by three disulfide bonds in a pattern identical ..
Chemical synthesis and orexigenic activity of rat/mouse relaxin-3
Mohammed Akhter Hossain, Craig M Smith, Philip J Ryan, Elena Buechler, Ross AD Bathgate, Andrew L Gundlach, John D Wade
The insulin-like peptide, relaxin-3 was first identified just a decade ago via a genomic database search and is now recognized to ..
Central relaxin-3 receptor (RXFP3) activation decreases anxiety- and depressive-like behaviours in the rat
Philip J Ryan, Elena Buechler, Fazel Shabanpoor, Mohammed Akhter Hossain, John D Wade, Andrew J Lawrence, Andrew L Gundlach
Relaxin-3 is a recently discovered neuropeptide and the results of earlier anatomical and pharmacological studies suggest it plays..
Sequential Formation of Regioselective Disulfide Bonds in Synthetic Peptides with Multiple Disulfide Bonds
Fazel Shabanpoor, Mohammed Akhter Hossain, Feng Lin, John D Wade
Numerous methods have been developed for the formation of disulfide bonds in recombinant DNA-derived and chemically synthesized pe..
Synthesis of fluorescent analogs of relaxin family peptides and their preliminary in vitro and in vivo characterization
Linda J Chan, Craig M Smith, Berenice E Chua, Feng Lin, Ross AD Bathgate, Frances Separovic, Andrew L Gundlach, Mohammed Akhter Hossain, John D Wade
Relaxin, a heterodimeric polypeptide hormone, is a key regulator of collagen metabolism and multiple vascular control pathways in ..
Total chemical synthesis of a heterodimeric interchain bis-lactam-linked Peptide: application to an analogue of human insulin-like Peptide 3.
John Karas, Fazel Shabanpoor, Mohammed Akhter Hossain, James Gardiner, Frances Separovic, John D Wade, Denis B Scanlon
Nonreducible cystine isosteres represent important peptide design elements in that they can maintain a near-native tertiary confor..
Identification of Key Residues Essential for the Structural Fold and Receptor Selectivity within the A-chain of Human Gene-2 (H2) Relaxin
Linda J Chan, K Johan Rosengren, Sharon L Layfield, Ross AD Bathgate, Frances Separovic, Chrishan S Samuel, Mohammed A Hossain, John D Wade
Human gene-2 (H2) relaxin is currently in Phase III clinical trials for the treatment of acute heart failure. It is a 53-amino aci..
Human relaxin-2: historical perspectives and role in cancer biology
Vinojini B Nair, Chrishan S Samuel, Frances Separovic, Mohammed Akhter Hossain, John D Wade
One of the most recognised and studied family of peptide hormones is the insulin superfamily. Within this family is the relaxin su..
Site-specific DOTA/europium-labeling of recombinant human relaxin-3 for receptor-ligand interaction studies
Wei-Jie Zhang, Xiao Luo, Ya-Li Liu, Xiao-Xia Shao, John D Wade, Ross AD Bathgate, Zhan-Yun Guo
Relaxin-3 (also known as INSL7) is a recently identified neuropeptide belonging to the insulin/relaxin superfamily. It has putativ..
Site-specific conjugation of a lanthanide chelator and its effects on the chemical synthesis and receptor binding affinity of human relaxin-2 hormone
Fazel Shabanpoor, Ross AD Bathgate, Alessia Belgi, Linda J Chan, Vinojini B Nair, John D Wade, Mohammed Akhter Hossain
Diethylenetriamine pentaacetic acid (DTPA) is a popular chelator agent for enabling the labeling of peptides for their use in stru..
Minimization of Human Relaxin-3 Leading to High-Affinity Analogues with Increased Selectivity for Relaxin-Family Peptide 3 Receptor (RXFP3) over RXFP1
Fazel Shabanpoor, Mohammad Alchter Hossain, Philip J Ryan, Alessia Belgi, Sharon Layfield, Martina Kocan, Suode Zhang, Chrishan S Samuel, Andrew L Gundlach, Ross AD Bathgate, Frances Separovic, John D Wade
Relaxin-3 is a neuropeptide that is implicated in the regulation of stress responses and memory. The elucidation of its precise ph..
The Minimal Active Structure of Human Relaxin-2
Mohammed Akhter Hossain, K Johan Rosengren, Chrishan S Samuel, Fazel Shabanpoor, Linda J Chan, Ross AD Bathgate, John D Wade
H2 relaxin is a peptide hormone associated with a number of therapeutically relevant physiological effects, including regulation o..
A simple approach for the preparation of mature human relaxin-3
Xiao Luo, Ya-Li Liu, Sharon Layfield, Xiao-Xia Shao, Ross AD Bathgate, John D Wade, Zhan-Yun Guo
Relaxin-3 (also known as INSL7) is the most recently identified member of the insulin-like family. It is predominantly expressed i..
Design and recombinant expression of insulin-like peptide 5 precursors and the preparation of mature human INSL5
Xiao Luo, Ross AD Bathgate, Wei-Jie Zhang, Ya-Li Liu, Xiao-Xia Shao, John D Wade, Zhan-Yun Guo
Insulin-like peptide 5 (INSL5) is a recently identified insulin superfamily member. Although it binds to and activates the G-prote..
Solid Phase Synthesis of an Analogue of Insulin, A0:R glargine, That Exhibits Decreased Mitogenic Activity
Seon-Yeong Kwak, Briony E Forbes, Yoon-Sik Lee, Alessia Belgi, John D Wade, Mohammed Akhter Hossain
Numerous analogues of insulin have been prepared over the past three decades for use in diabetic therapy. However, only two long-a..
The chemically synthesized human relaxin-2 analog, B-R13/17K H2, is an RXFP1 antagonist
Mohammed Akhter Hossain, Chrishan S Samuel, Claudia Binder, Tim D Hewitson, Geoffrey W Tregear, John D Wade, Ross AD Bathgate
Relaxin is a pleiotropic hormone which exerts its biological functions through its G-protein coupled receptor, RXFP1. While relaxi..
Structure of human insulin-like peptide 5 and characterization of conserved hydrogen bonds and electrostatic interactions within the relaxin framework
Linda M Haugaard-Jonsson, Mohammed Akhter Hossain, Norelle L Daly, David J Craik, John D Wade, K Johan Rosengren
INSL5 (insulin-like peptide 5) is a two-chain peptide hormone related to insulin and relaxin. It was recently discovered through s..
Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity
Mohammed Akhter Hossain, K Johan Rosengren, Suode Zhang, Ross AD Bathgate, Geoffrey W Tregear, Bianca J van Lierop, Andrea J Robinson, John D Wade
Replacement of disulfide bonds with non-reducible isosteres can be a useful means of increasing the in vivo stability of a protein..
Structure and Activity in the Relaxin Family of Peptides
Geoffrey W Tregear, Ross AD Bathgate, Mohammed Akhter Hossain, Feng Lin, Suode Zhang, Fazel Shabanpoor, Daniel J Scott, Sherie Ma, Andrew L Gundlach, Chrishan S Samuel, John D Wade
The availability of improved peptide synthesis procedures, convenient and sensitive assays for receptor binding and activation, to..
The Structural and Functional Role of the B-chain C-terminal Arginine in the Relaxin-3 Peptide Antagonist, R3(B Delta 23-27)R/I5
Mohammed Akhter Hossain, Ross AD Bathgate, K Johan Rosengren, Fazel Shabanpoor, Suode Zhang, Feng Lin, Geoffrey W Tregear, John D Wade
Relaxin-3, a member of the insulin superfamily, is involved in regulating stress and feeding behavior. It is highly expressed in t..