Enhancing the clinical potential of relaxin

Engineering of a Biologically Active Insulin Dimer.

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

2021-11-19

The growing epidemic of diabetes means that there is a need for therapies that are more efficacious, safe, and convenient. Here, w..

The Chemical Synthesis of Insulin: An Enduring Challenge

John A Karas, John D Wade, Mohammed Akhter Hossain

2021-04-28

The pancreatic peptide hormone insulin, first discovered exactly 100 years ago, is essential for glycemic control and is used as a..

Total Chemical Synthesis of a Nonfibrillating Human Glycoinsulin

Mohammed Akhter Hossain, Rio Okamoto, John A Karas, Praveen Praveen, Mengjie Liu, Briony E Forbes, John D Wade, Yasuhiro Kajihara

2020-01-22

Glycosylation is an accepted strategy to improve the therapeutic value of peptide and protein drugs. Insulin and its analogues are..

Relaxin-3 receptor (RXFP3) activation in the nucleus of the solitary tract modulates respiratory rate and the arterial chemoreceptor reflex in rat

Werner I Furuya, Rishi R Dhingra, Andrew L Gundlach, Mohammad Akhter Hossain, Mathias Dutschmann

2020-01-01

The neuropeptide relaxin-3 is expressed by the pontine nucleus incertus. Relaxin-3 and synthetic agonist peptides modulate arousal..

Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4

Praveen Praveen, Ross AD Bathgate, Mohammed Akhter Hossain

2019-11-28

Insulin-like peptide 5 (INSL5) is a very important pharma target for treating human conditions such as anorexia and diabetes. Howe..

Relaxin family peptides: structure-activity relationship studies

Nitin A Patil, K Johan Rosengren, Frances Separovic, John D Wade, Ross AD Bathgate, Mohammed Akhter Hossain

2017-05-01

The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family..

Total Chemical Synthesis of an Intra-A-Chain Cystathionine Human Insulin Analogue with Enhanced Thermal Stability

John A Karas, Nitin A Patil, Julien Tailhades, Marc-Antoine Sani, Denis B Scanlon, Briony E Forbes, James Gardiner, Frances Separovic, John D Wade, Mohammed Akhter Hossain

2016-11-14

Despite recent advances in the treatment of diabetes mellitus, storage of insulin formulations at 4 °C is still necessary to minim..

The C-terminus of the B-chain of human insulin-like peptide 5 is critical for cognate RXFP4 receptor activity

Nitin A Patil, Ross AD Bathgate, Martina Kocan, Sheng Yu Ang, Julien Tailhades, Frances Separovic, Roger Summers, Johannes Grosse, Richard A Hughes, John D Wade, Mohammed Akhter Hossain

2016-04-01

Insulin-like peptide 5 (INSL5) is an orexigenic peptide hormone belonging to the relaxin family of peptides. It is expressed prima..

Engineering of a Novel Simplified Human Insulin-Like Peptide 5 Agonist

Nitin A Patil, Richard A Hughes, K Johan Rosengren, Martina Kocan, Sheng Yu Ang, Julien Tailhades, Frances Separovic, Roger J Summers, Johannes Grosse, John D Wade, Ross AD Bathgate, Mohammed Akhter Hossain

2016-03-10

Insulin-like peptide 5 (INSL5) has recently been discovered as only the second orexigenic gut hormone after ghrelin. As we have pr..

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

2016-01-18

The inhibition of the G protein-coupled receptor, relaxin family peptide receptor 1 (RXFP1), by a small LDLa protein may be a pote..

A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1

Mohammed Akhter Hossain, Martina Kocan, Song T Yao, Simon G Royce, Vinojini B Nair, Christopher Siwek, Nitin A Patil, Ian P Harrison, K Johan Rosengren, Stavros Selemidis, Roger J Summers, John D Wade, Ross AD Bathgate, Chrishan S Samuel

2016-01-01

Human gene-2 relaxin (H2 relaxin) is a pleiotropic hormone with powerful vasodilatory and anti-fibrotic properties which has led t..

Solution Structure, Aggregation Behavior, and Flexibility of Human Relaxin-2

Linda M Haugaard-Kedstrom, Mohammed Akhter Hossain, Norelle L Daly, Ross AD Bathgate, Ernst Rinderknecht, John D Wade, David J Craik, K Johan Rosengren

2015-03-01

Relaxin is a member of the relaxin/insulin peptide hormone superfamily and is characterized by a two-chain structure constrained b..

Chemically synthesized dicarba H2 relaxin analogues retain strong RXFP1 receptor activity but show an unexpected loss of in vitro serum stability

Mohammed Akhter Hossain, Linda M Haugaard-Kedstroem, K Johan Rosengren, Ross AD Bathgate, John D Wade

2015-01-01

Peptides and proteins are now acknowledged as viable alternatives to small molecules as potential therapeutic agents. A primary li..

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

2015-01-01

Human (H2) relaxin is a two-chain peptide member of the insulin superfamily and possesses potent pleiotropic roles including regul..

Synthetic relaxins

Mohammed Akhter Hossain, John D Wade

2014-10-01

The relaxin subfamily of peptides within the human insulin superfamily consists of seven members including relaxin-2 and relaxin-3..

2-Nitroveratryl as a Photocleavable Thiol-Protecting Group for Directed Disulfide Bond Formation in the Chemical Synthesis of Insulin

John A Karas, Denis B Scanlon, Briony E Forbes, Irina Vetter, Richard J Lewis, James Gardiner, Frances Separovic, John D Wade, Mohammed A Hossain

2014-07-28

Chemical synthesis of peptides can allow the option of sequential formation of multiple cysteines through exploitation of judiciou..

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

2013-12-12

Insulin-like peptide 5 (INSL5) is a complex two-chain peptide hormone constrained by three disulfide bonds in a pattern identical ..

C-Terminus of the B-Chain of Relaxin-3 Is Important for Receptor Activity

Fazel Shabanpoor, Ross AD Bathgate, John D Wade, Mohammed Akhter Hossain

2013-12-11

Human relaxin-3 is a neuropeptide that is structurally similar to human insulin with two chains (A and B) connected by three disul..

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

2013-06-01

The insulin-like peptide, relaxin-3 was first identified just a decade ago via a genomic database search and is now recognized to ..

Preliminary Structure-Function Relationship Studies on Insulin-Like Peptide 5 (INSL5)

Alessia Belgi, Ross AD Bathgate, Geoffrey W Tregear, John D Wade, Mohammed Akhter Hossain

2013-03-01

Insulin-like peptide 5 (INSL5) is a two-chain, three-disulfide bonded member of insulin/relaxin superfamily of peptides that inclu..

The Importance of Tryptophan B28 in H2 Relaxin for RXFP2 Binding and Activation

Linda J Chan, John D Wade, Frances Separovic, Ross AD Bathgate, Mohammed Akhter Hossain

2013-03-01

H2 relaxin (relaxin) is a member of the insulin-relaxin superfamily and exhibits several non-reproductive functions in addition to..

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

2013-01-01

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

2013-01-01

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

2012-11-30

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

2012-09-01

One of the most recognised and studied family of peptide hormones is the insulin superfamily. Within this family is the relaxin su..