Dist Prof Margaret Anne Brimble

MSc (Auckland), PhD (Southampton, UK)

Research | Current

Natural products have long been regarded as ‘nature’s medicine chest’ providing a rich source of lead compounds as invaluable platforms for developing front-line drugs. Our research focuses on making and modifying naturally occurring bioactive compounds that have been isolated from plants, animal tissue, microbes or marine and soil organisms, which are rare or hard to isolate in abundance. These compounds provide rich and diverse chemical structures that challenge the synthetic chemist to develop new flexible synthetic methodology for their construction. The preparation of synthetic analogues of the natural compound may improve the biological activity and provide an understanding of the mechanism of action of the naturally occurring compound.

Our research group also comprises a national peptide, peptidomimetic and glycopeptide chemistry facility that occupies a world-class laboratory in the Institute for Innovation in Biotechnology. The peptide synthesis laboratory supports growth in the burgeoning area of peptide therapeutics that is growing at twice the rate of small molecule therapeutics by engaging with the local biotech community to develop viable drug candidates based on peptide leads. An example is the development of NNZ2566 for Neuren Pharmaceuticals that is currently in phase 2b clinical trials for traumatic brain injury and was successful in phase 2 clinical trials for Rett Syndrome and has been given the name trofinetide by the WHO. Our laboratory has also been licensed by medsafe for the GMP manufacture of peptides for the clinical trial of melanoma vaccines (MELVAC trial).  The synthesis of natural product peptides containing unnatural amino acids, depsipeptides, cyclic peptides and natural proteins that exhibit potent antimicrobial activity, is one theme in our peptide chemistry laboratory. Analogues of the natural peptides are then synthesised to either simplify or stabilise the molecule with the aim of producing a more potent analogue. The ability to combine contemporary organic reactions such as cross-metathesis, “peptide stapling”, click chemistry, thiol-ene chemistry and the preparation of unnatural amino-acid building blocks with modern solid phase synthesis methods provides a powerful peptidomimetic platform to combat the problem of increasing resistance to existing antibiotics.  The peptide chemistry group also synthesizes peptide-based hydrogels with applications in bionanotechnology and regenerative medicine.

Current projects

  • Synthesis and Medicinal Chemistry of Natural Product Shellfish Toxins: New Pharmacological Probes for Treatment of Cardiovascular and Neurodegenerative Diseases and Anticancer Agents (with Dr Dan Furkert)
  • Drug Discovery Inspired by Traditional Chinese Medicines (TCM): Synthesis of Complex Bioactive Compounds as Treatments for Diabetes (with Dr Dan Furkert)
  • Asymmetric Synthesis of Benzannulated Spiroketals: Towards Novel Telomerase Inhibitors Based on the Rubromycin Family of Antibotics (with Dr Dan Furkert)
  • Total Synthesis and Structural Elucidation of the Anticancer Agent Callyspongiolide (with Dr Dan Furkert)
  • Synthesis of Pyrrole-containing Natural Products as Antibacterial Agents and Anti TB Agents (with Prof Greg Cook, University of Otago and Maurice Wilkins Centre for Molecular Biodiscovery)
  • Synthesis of the Anti-TB Agents the Peniphenones (with Dr Dan Furkert)
  • Medicinal Chemistry of Stable Analogues of Isochorismate: Antibiotics for Control of  Mycobacterium tuberculosis (TB) (with Dr Dan Furkert and Assoc. Prof Shaun Lott, Maurice Wilkins Centre for Molecular Biodiscovery)
  • Synthesis of Pyranonaphthoquinone Antibiotics as Anticancer Agents and Agents to Treat Viral Diseases
  • Understanding the Molecular Basis of Cannabinoid CB1 Receptor Ligand Binding for Modulation of CNS Cell Signalling Pathways (with Dr Dan Furkert and Assoc. Prof. Michelle Glass, Pharmacology, FMHS)
  • Towards Effective Antibody-Directed Cytotoxins (ADCs): Probing The Influence of Unnatural Amino Acid Components of Culicinin D, a Marine Natural Product (with Assoc. Prof. Adam Patterson and Dr Jeff Smaill, Maurice Wilkins Centre for Molecular Biodiscovery)
  • Synthesis of New Generation Lipopeptide-based Antibiotics Using Patented CLiPA Technology (with Dr Paul Harris, School of Biological Sciences)
  • Synthesis and Development of Antimicrobial Peptides Based on Teixobactin in the Fight Against Bacterial Resistance (with Dr Andrew Wadsworth, School of Biological Sciences)
  • Use of CH Activation for the Efficient Synthesis of Novel Cross-linked Amino Acids in the Novel Macrocyclic Peptide, Streptide – A Quorum Sensing Signaling Agent (with Dr Dan Furkert and Dr Paul Harris, School of Biological Sciences)
  • Synthesis of the Antimicrobial Bacteriocin Peptide Glycocin F and Analogues Thereof (with Assoc. Prof. Gillian Norris, Massey University)
  • Synthesis of Amylin Mimics (Pramlitide) as a Treatment for Diabetes (with A/Prof Debbie Hay, School of Biological Sciences)
  • Synthesis of Peptide Hormones and Natural Products (e.g. the Dianthins) for the Treatment of Diabetes and Osteoporosis (with Prof Jill Cornish, Auckland Bone Biology Group)
  • Synthesis of Advanced Glycation Endproduct (AGE Peptides) as Agents to Study Metabolic Disorders and Diabetic Heart Failure (with Dr. Kim Mellor, Department of Physiology and Prof Lea Delbridge, Department of Physiology, University of Melbourne)
  • Synthesis of GlycoPeptides and Lipopeptides as Novel Adjuvants for Cancer Vaccines (with Prof. Rod Dunbar, Maurice Wilkins Centre for Molecular Biodiscovery)
  • Synthesis of Functionalized Self-Assembling Peptides as Hydrogels for Regenerative Medicine  (with Prof Jill Cornish, Auckland Bone Biology Group)

Find more information about Margaret's research on the Brimble Group website.


2015: IUPAC Distinguished Women in Chemistry/Chemical Engineeering Award; University of Auckland Vice-Chancellor’s Commercialization Medal; Senior Fellowship Award International Society of Heterocyclic Chemistry

2014: Westpac Trust Women of Influence Award (Science and Innovation)

2012: Queen’s Honour - Companion of the New Zealand Order of Merit for Service to Science; Appointed Distinguished Professor at The University of Auckland; RSNZ – Rutherford Medal (Exceptional Contributions to NZ Science & Technology); RSNZ – Hector Medal (Outstanding Contributions to Chemical Sciences); RSNZ – MacDiarmid Medal (Outstanding Scientific Research for Human Benefit)

2011: RACI (Aus) Adrien Albert Award - Medicinal Chemistry; Dean’s Award for Excellence in Postgraduate Supervision

2010: RSC (UK): Natural Products Chemistry Award; Simonsen Lectureship; Editorial Board Award

2008: World Class New Zealander Award (Research, Science, Technology & Academia), Kea and NZ Trade & Enterprise

2007: L'ORÉAL-UNESCO Women in Science Laureate Asia/Pacific

2004: Queen’s Honour - Member New Zealand Order of Merit Service to Science; RSNZ - James Cook Research Fellowship; Novartis Chemistry Award and Lectureship; Inaugural UK Royal Society Rosalind Franklin International Lectureship

Areas of expertise

Expertise: Inventor – Trofinitide (NNZ2566) – first drug for Rett Syndrome; in phase 2 clinical trials for Traumatic Brian Injury, Concussion, Fragile X Syndrome (Neuren Pharmaceuticals); Organic Synthesis; Medicinal Chemistry; Drug Development; Natural Products; Agrochemistry; GMP synthesis melanoma vaccines (phase 1 trial); Consultant/Expert Witness - pharmaceutical companies.

Interests: Synthesis of: bioactive natural products and traditional Chinese medicines; rhinovirus 3C protease inhibitors; telomerase inhibitors; antimicrobial peptides; cell penetrating peptides; peptidomimetics; alkaloids as neuroprotective agents; glycopeptides, lipopeptides, cGMP peptides as vaccine components; fish antifreeze peptides; agrochemicals. Organocatalysis. Synthesis of neo-glycopeptides, neo-phosphopeptides, neo-lipopeptides using click chemistry and olefin metathesis. Synthesis of small proteins, glycopolymers and hydrogels.

Committees/Professional groups/Services

Distinguished Professor, Chair of Organic and Medicinal Chemistry, Director of Medicinal Chemistry, Chair of the Royal Society of New Zealand Rutherford Foundation, Vice-President of Organic and Biomolecular Division of the International Union of Pure and Applied Chemistry, Member of the European Research Council PE5 panel for Synthetic Chemistry and Materials Science, Member of International Society of Heterocyclic Chemistry, Principle Investigator and member of the management committee of Maurice Wilkins Centre for Molecular Biodiscovery, Principal Investigator in Brain Research NZ.


Selected publications and creative works (Research Outputs)

  • Shirley, H. J., Jamieson, M. L., Brimble, M. A., & Bray, C. D. (2018). A new family of sesterterpenoids isolated around the Pacific Rim. Natural product reports10.1039/c7np00049a
    Other University of Auckland co-authors: Megan Jamieson
  • Alexander, S. R., Williams, G. M., Brimble, M. A., & Fairbanks, A. J. (2018). A double-click approach to the protecting group free synthesis of glycoconjugates. Org Biomol Chem10.1039/c8ob00072g
    Other University of Auckland co-authors: Geoffrey Williams
  • Garelja, M. L., Walker, C. A., Siow, A., Yang, S. H., Harris, P. W. R., Brimble, M. A., ... Hay, D. L. (2018). Receptor Activity Modifying Proteins Have Limited Effects on the Class B G Protein-Coupled Receptor Calcitonin Receptor-Like Receptor Stalk. Biochemistry, 57 (8), 1410-1422. 10.1021/acs.biochem.7b01180
    Other University of Auckland co-authors: Sung Hyun Yang, Joseph Gingell, Debbie Hay, Michael Garelja, Paul Harris
  • Siow, A., Opiyo, G., Kavianinia, I., Li, F. F., Furkert, D. P., Harris, P. W. R., & Brimble, M. A. (2018). Total Synthesis of the Highly N-Methylated Acetylene-Containing Anticancer Peptide Jahanyne. Organic letters, 20 (3), 788-791. 10.1021/acs.orglett.7b03925
    Other University of Auckland co-authors: Daniel Furkert, Iman Kavianinia, Paul Harris
  • Gasser, O., Sharples, K. J., Barrow, C., Williams, G. M., Bauer, E., Wood, C. E., ... Jones, J. (2018). A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients. Cancer immunology, immunotherapy : CII, 67 (2), 285-298. 10.1007/s00262-017-2085-9
    Other University of Auckland co-authors: Geoffrey Williams, Michael Findlay, Rod Dunbar
  • Evans, G. L., Furkert, D. P., Abermil, N., Kundu, P., de Lange, K. M., Parker, E. J., ... Lott, J. S. (2018). Anthranilate phosphoribosyltransferase: Binding determinants for 5'-phospho-alpha-d-ribosyl-1'-pyrophosphate (PRPP) and the implications for inhibitor design. Biochimica et Biophysica Acta - Proteins and Proteomics, 1866 (2), 264-274. 10.1016/j.bbapap.2017.08.018
    Other University of Auckland co-authors: Daniel Furkert, Edward Baker, Shaun Lott
  • Zhang, S., De Leon Rodriguez, L. M., Leung, I. K. H., Cook, G. M., Harris, P. W. R., & Brimble, M. A. (2018). Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic Peptide Bearing a Rare Rigidifying (Z)-2,3- Diaminoacrylamide Moiety. Angewandte Chemie (International ed. in English)10.1002/anie.201712792
    Other University of Auckland co-authors: Ivanhoe Leung, Paul Harris
  • Amso, Z., Bisset, S. W., Yang, S. H., Harris, P. W. R., Wright, T. H., Navo, C. D., ... Brimble, M. A. (2018). Total chemical synthesis of glycocin F and analogues: S-glycosylation confers improved antimicrobial activity. Chemical Science, 9 (6), 1686-1691. 10.1039/c7sc04383j
    Other University of Auckland co-authors: Sung Hyun Yang, Paul Harris


Contact details

Alternative contact

Correct Location:
Level 7, Room 301-731B
Auckland 1010
New Zealand

Primary location

Level 7, Room 731B
New Zealand

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