Novel insulin to treat diabetes

Grant number: 1023321 | Funding period: 2012 - 2015

Completed

Abstract

The glucose regulatory hormone, insulin, remains the only treatment for type I diabetes and up to 30% of type II diabetes, both of which are among the world’s fastest growing chronic diseases today. Because insulin, if taken orally, would be broken down quickly, it has usually been given by injection. This project will develop novel chemical methods for the efficient preparation of novel insulin therapeutics with improved stability and oral bioavailability for prolonged treatment of patients.

Related publications (23)

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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

2021-12-09

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

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The Chemical Synthesis of Insulin: An Enduring Challenge

John A Karas, John D Wade, Mohammed Akhter Hossain

2021-03-09

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

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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..

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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..

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Traceable Peptidic Ligands that Target Ghrelin Receptors

Mengjie Liu, John Wade, Mohammed Akhter Hossain

2020-01-01

Ghrelin is a 28-amino acid octanoylated peptide hormone that is implicated in many physiological and pathophysiological processes...

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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..

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Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides

Nitin A Patil, John A Karas, John D Wade, Mohammed Akhter Hossain, Julien Tailhades

2019-06-26

Structure-activity relationship studies are a highly time-consuming aspect of peptide-based drug development, particularly in the ..

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Single chain peptide agonists of relaxin receptors

Praveen Praveen, Martina Kocan, Adam Valkovic, Ross Bathgate, Mohammed Akhter Hossain

2019-05-01

There are seven human relaxin family peptides that have two chains (A and B) and three disulfide bonds. The target receptors for f..

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Challenges in the design of insulin and relaxin/insulin-like peptide mimetics

Mohammed Akhter Hossain, Ross AD Bathgate

2018-06-01

Peptidomimetics are designed to overcome the poor pharmacokinetics and pharmacodynamics associated with the native peptide or prot..

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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

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

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A One-Pot Chemically Cleavable Bis-Linker Tether Strategy for the Synthesis of Heterodimeric Peptides

Nitin A Patil, Julien Tailhades, John A Karas, Frances Separovic, John D Wade, Mohammed Akhter Hossain

2016-11-14

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A One-Pot Chemically Cleavable Bis-Linker Tether Strategy for the Synthesis of Heterodimeric Peptides

Nitin A Patil, Julien Tailhades, John A Karas, Frances Separovic, John D Wade, Mohammed Akhter Hossain

2016-11-14

Heterodimeric peptides linked by disulfide bonds are attractive drug targets. However, their chemical assembly can be tedious, tim..

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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..

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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..

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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..

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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..

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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..

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Cellular Disulfide Bond Formation in Bioactive Peptides and Proteins

Nitin A Patil, Julien Tailhades, Richard Anthony Hughes, Frances Separovic, John D Wade, Mohammed Akhter Hossain

2015-01-01

Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides o..

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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..

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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..

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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 ..

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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..

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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..