Novel insulin to treat diabetes
Grant number: 1023321 | Funding period: 2012 - 2015
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 (20)
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
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
The neuropeptide relaxin-3 is expressed by the pontine nucleus incertus. Relaxin-3 and synthetic agonist peptides modulate arousal..
Relaxin family peptides: structure-activity relationship studies
Nitin A Patil, K Johan Rosengren, Frances Separovic, John D Wade, Ross AD Bathgate, Mohammed Akhter Hossain
The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family..
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
Heterodimeric peptides linked by disulfide bonds are attractive drug targets. However, their chemical assembly can be tedious, tim..
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
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
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
Insulin-like peptide 5 (INSL5) has recently been discovered as only the second orexigenic gut hormone after ghrelin. As we have pr..
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
Human gene-2 relaxin (H2 relaxin) is a pleiotropic hormone with powerful vasodilatory and anti-fibrotic properties which has led t..
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
Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides o..
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
Peptides and proteins are now acknowledged as viable alternatives to small molecules as potential therapeutic agents. A primary li..
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
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
Insulin-like peptide 5 (INSL5) is a complex two-chain peptide hormone constrained by three disulfide bonds in a pattern identical ..
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
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
H2 relaxin (relaxin) is a member of the insulin-relaxin superfamily and exhibits several non-reproductive functions in addition to..