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.

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 diarrhoea
  • Antimicrobial peptides for treating bacterial infection

  • Solid-phase peptide synthesis
  • Regioselective disulfide bond formation
  • Circular dichroism studies
  • Peptide-drug conjugation
  • Computational chemistry
  • Molecular pharmacology
  • Solution NMR
  • Animal models of diarrhoea and constipation, fibrosis and heart failure

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 team

Research team head

Team members

Research fellows

  • Dr Chaitra Chandrashekar

PhD students

  • Hongkang Wu
  • Yi Kee Yoong
  • Sam Mohammed

Honours students

  • Shagun Batish
  • Ahmed Farhan Labib

Selected publications

  • Liu M, White BF, Praveen P, Li W, Lin F, Wu H, Li R, Delaine C, Forbes BE, Wade JD and Hossain MA (2021), ‘Engineering of a biologically active insulin dimer’, Journal of Medicinal Chemistry, 64(23):17448–17454, doi:10.1021/acs.jmedchem.1c01594
  • Karas JA, Wade JD and Hossain MA (2021), ‘The chemical synthesis of insulin: an enduring challenge, Chemical Reviews, 121(8):4531–4560, doi:10.1021/acs.chemrev.0c01251
  • Hossain MA, Okamoto R, Karas JA, Praveen P, Liu M, Forbes BE, Wade JD and Kajihara Y (2020), Total chemical synthesis of a non-fibrillating human glycoinsulin, Journal of the American Chemical Society, 142(3):1164–1169, doi:10.1021/jacs.9b11424
  • Patil NT, Tailhades J, Karas JA, Separovic F, Wade JD and Hossain MA (2016), ‘A one‐pot chemically cleavable bis‐linker tether strategy for the synthesis of heterodimeric peptides’, Angewandte Chemie, 55(47):14552–14556, doi:10.1002/anie.201604733
  • Karas JA, Patil NA, Tailhades J, Sani M, Scanlon DB, Forbes BE, Gardiner J, Separovic F, Wade JD and Hossain MA (2016), ‘Total chemical synthesis of an intra‐A‐chain cystathionine human insulin analogue with enhanced thermal stability, Angewandte Chemie International Edition, 55(47):14743–14747, doi:10.1002/anie.201607101‌

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