Insulin Peptides Group
Our group focuses on addressing problems of medicinal significance. We use modern solid and solution phase synthesis technologies, and developing new chemical methods, for scaling up the production of insulin, insulin-like molecules and antimicrobial peptides.
Our approach is multidisciplinary, covering chemistry, computational chemistry, structural biology, pharmacology, and physiology. By combining our varied skills and expertise, we hope to design and develop peptide-based tools and drug leads for pre-clinical evaluation in rodent models of diabetes, obesity, fibrosis, heart failure, chronic pain, stress and anxiety, alcohol addiction, colon motility disorders, and bacterial infection.
About our research
One of our key specialties is the generation of single-chain alternatives to complex two-chain peptides of the relaxin and insulin-like peptide families. One example of this is the generation of a single-chain analogue, B7-33, of complex two-chain human relaxin-2. B7-33 is an easily synthesised single-chain peptide but retains the beneficial cell signalling capacities and biological effects of human relaxin-2 (e.g. antifibrotic and heart-protective function). The approach of generating single-chain analogues is challenging but ultimately has yielded several single-chain analogues of complex 2-chain bioactive peptides such as H3 relaxin, INSL3, and INSL5, which we have subsequently used as scaffolds to explore stapling strategies to stabilise the peptides, and strategies to improve receptor binding, potency, and specificity. Our novel single-chain peptides (agonists and antagonists) are shown to have enormous therapeutic potential for a range of diseases including diabetes, obesity, fibrosis, and colon motility disorders.
Research interests
- Insulin and mimetics for treating diabetes.
- H2 relaxin and mimetic agonists for treating fibrosis and heart failure, antagonists for treating prostate cancer.
- H3 relaxin and mimetic agonists for treating chronic pain, stress, and anxiety, antagonists for treating alcohol addiction.
- INSL5 for treating colon motility disorders such as agonists for constipation and antagonists for diarrhea.
- Antimicrobial peptides for treating bacterial infection.
Techniques
- Solid-phase peptide synthesis
- Regioselective disulfide bond formation
- Circular dichroism studies
- Peptide-drug conjugation
- Computational chemistry
- Molecular pharmacology
- Solution NMR
- Animal models of diarrhea and constipation
- Animal models of fibrosis and heart failure
Research team
Research team head
Group Head
Team members
Research fellows
- Dr Thomas N. G. Handley
- Dr Chaitra Chandrashekar
PhD students
- Hongkang Wu
- Yi Kee Yoong
- Sam Mohammed
Honours students
- Shagun Batish
- Krijma D’Costa
- Maxwell Alder
- Ahmed Farhan Labib
Publications
- Liu, M., White, B.F., Praveen, P., Li, W., Lin, F., Wu, H., Li, R., Delaine, C., Forbes, B.E., Wade, J.D. and Hossain, M.A. (2021). Engineering of a Biologically Active Insulin Dimer. Journal of Medicinal Chemistry, [online] 64(23), pp.17448–17454. doi:https://doi.org/10.1021/acs.jmedchem.1c01594.
- Karas, J.A., Wade, J.D. and Hossain, M.A. (2021). The Chemical Synthesis of Insulin: An Enduring Challenge. Chemical Reviews, 121(8), pp.4531–4560. doi:https://doi.org/10.1021/acs.chemrev.0c01251.
- Mohammed Akhter Hossain, Okamoto, R., Karas, J.A., Praveen Praveen, Liu, M., Forbes, B.E., Wade, J.D. and Yasuhiro Kajihara (2020). Total Chemical Synthesis of a Nonfibrillating Human Glycoinsulin. Journal of the American Chemical Society, 142(3), pp.1164–1169. doi:https://doi.org/10.1021/jacs.9b11424.
- Patil, N.T., Julien Tailhades, Karas, J.A., Separovic, F., Wade, J.D. and Mohammed Akhter Hossain (2016). A One‐Pot Chemically Cleavable Bis‐Linker Tether Strategy for the Synthesis of Heterodimeric Peptides. Angewandte Chemie, 55(47), pp.14552–14556. doi:https://doi.org/10.1002/anie.201604733.
- Karas, J.A., Patil, N.A., Tailhades, J., Sani, M., Scanlon, D.B., Forbes, B.E., Gardiner, J., Separovic, F., Wade, J.D. and Hossain, M.A. (2016). Total Chemical Synthesis of an Intra‐A‐Chain Cystathionine Human Insulin Analogue with Enhanced Thermal Stability. Angewandte Chemie International Edition, 55(47), pp.14743–14747. doi:https://doi.org/10.1002/anie.201607101.
Contact us
Professor Akhter Hossain
Group Head
[email protected]