Dr Paul William Richard Harris

1997-00 Ph.D., in Chemistry, the University of Auckland 1995-96 M.Sc., Chemistry with First Class Honours, the University of Auckland 1992-94 B.Sc., Chemistry, the University of Auckland

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Associate Professor

Biography

2016-      Senior Research Fellow (above the Bar), School of Biological Sciences, the University of Auckland

2009-15, Senior Research Fellow, School of Chemical Sciences, the University of Auckland

2008-09  Research Fellow, Department of Chemistry, the University of Auckland

2001-08 Research Fellow, Neuren Pharmaceuticals Ltd (spin out company from the University of Auckland)

2000-01 Postdoctoral Research Fellow, Royal Melbourne Institute of Technology University (RMIT), Australia.

2000        C.N.R.S. Postdoctoral Fellow, Universite Pierre et Marie Curie, Paris, France

Research | Current

Current research interests are: 

Boron neutron capture therapy (BNCT)

Worldwide, there are currently over 17 million people with cancer and in NZ cancer affects more people than all other diseases combined.  The traditional 3-pronged approach, surgery, chemotherapy and radiotherapy has been the mainstay of combating cancer.  There is a critical need to develop new technology in cancer therapeutics.  Innovative therapies such charged particle therapy (CPT) is the fastest growing field of cancer radiotherapy that confines high levels of energy to the tumour site, sparing damage to healthy tissue. Boron Neutron Capture Therapy (BNCT) is based upon neutron capture by non-radioactive boron-10 to generate the charged particle in situ.  Irradiation of boron-10 results in a nuclear fission reaction generating destructively charged He-4 α-particles, whose energy is confined to a single cell, which restricts lethal damage only to the targeted tumour cell.  Technological advances from nuclear-based neutron beam accelerators to safe, effective electricity–based generators, are now here but innovations in chemical components that can deliver boron-10 exclusively to cancerous sites are scarce.  This project aims to develop peptide boron-10 carriers capable of achieving therapeutic delivery to multiple cancer types thus realising the potential of BNCT. This is primarily a chemical synthesis project but evaluation of boron-containing compounds will inform the synthesis direction.

See “Boron delivery agents for neutron capture therapy of cancer” Barth, R. F.; Mi, P.; Yang, W. Cancer Commun (Lond) 2018, 38, 35.

Fast flow (peptide) synthesis

Chemical synthesis to construct molecules to use for human medicines employ traditional, century old techniques, such as flasks, stirrers, reflux condensers and are a demanding, labour-intensive process.  While these methods have served the discipline well, new technologies, such as flow chemistry, are needed that can enhance the field of medicinal chemistry that serves to treat human disease. Flow chemistry, the science of using automation to conduct chemical reactions in a safe, reproducible and reliable fashion, is positioned to impact research laboratories and the pharmaceutical industry. This methodology can take time-consuming laboratory “bench reactions” and transform them into an efficient, programmable chemical process that produces substantially increased quantities of a molecule in a fraction of the time required. This project will involve building a flow chemistry apparatus from the "ground up" using easily interchangeable components, controlled by simple microprocessors (e.g. Raspberry Pie) and basic computing. This would suit students with a healthy interest in computer science/networking and chemistry.

See “The renascence of continuous-flow peptide synthesis - an abridged account of solid and solution-based approaches”. Gordon, C. P. Org. Biomol. Chem. 2018, 16, 180-196

Synthesis of novel peptide antibiotics

Antimicrobial-resistant bacteria has been recognised by the WHO as one of the greatest threats to humankind, and infectious diseases rank as the second most common cause of death worldwide. Without urgent action, most routine health treatments could be complicated by life threatening infections that are unable to be treated with existing antimicrobials. The projections are that as many as10 million people per annum will succumb to bacterial infections by 2050. Naturally occurring antimicrobial peptides (AMPs), the host-defence molecules of most living organisms, have shown great promise as potential antibiotic candidates. They are especially promising due to the unique and non-specific bactericidal mechanism of action. This project involves the chemical synthesis of naturally-occurring peptides that can then be modified using medicinal chemistry techniques to improve their bioactivity and minimising associated side effects. Students will become well-versed in chemical synthesis and have the opportunity to evaluate their compounds for activity against Gram-negative and positive bacteria

See “Antimicrobial Peptides: An Introduction”  Haney E.F., Mansour S.C., Hancock R.E.W. (2017). In: Hansen P. (eds) Antimicrobial Peptides. Methods in Molecular Biology, vol 1548. Humana Press, New York, NY

Glycoprotein mimetics

Glycoproteins, proteins that are decorated with sugars (glycans) on their surface, are fast becoming one of the most important protein-based drugs in the 21st century. To be therapeutically useful, the sugars need to be correctly positioned on the protein and improve stability and solubility. Changes in glycan coverage can greatly affect the efficacy, half-life, and immunogenicity of proteins as therapeutics.  The glycan biosynthetic process in cells produces proteins containing 10 different monosaccharides, with varied sequence order, branching and length Glycoproteins produced biosynthetically will always afford heterogeneous mixes of beneficial and undesirable glycoforms which compromises their use as therapeutics.  This project will employ sophisticated chemical techniques to manipulate therapeutic proteins, by precisely controlling the location of the glycans, thereby developing a new stratagem in glycoprotein biodrugs

See “A Synthetic Approach to ‘Click’ Neoglycoprotein Analogues of EPO Employing One-pot Native Chemical Ligation and CuAAC Chemistry” D.J. Lee, A.J. Cameron, T.H. Wright, P.W.R. Harris, M.A. Brimble, Chem. Sci., 2019, 10, 815-828

Postgraduate supervision

Current PhD students

Danielle Paterson

Georgina Howard

Victor Yim

Jakob Gaar

Aakanksha Rani

Elyse Williams

Nadiia Kovalenko

Yann Hermant

Saawan Kumar

Marzieh Ahangarpour

Christy Siu

Johanes Kevin Kasim

Yubing Mao

Oscar Shepperson

Yuxin Wang

Current BSc Hons students

Casey Park

Juliana Tong

Anna Parsons

Areas of expertise

Organic chemistry; peptide chemistry; solid phase synthesis; high performance liquid chromatography; liquid chromatography mass spectrometry. Native chemical ligation. Protein synthesis

Selected publications and creative works (Research Outputs)

  • Cameron, A. J., Harris, P. W. R., & Brimble, M. A. (2020). On-Resin Preparation of Allenamidyl Peptides: A Versatile Chemoselective Conjugation and Intramolecular Cyclisation Tool. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION10.1002/anie.202004656
    Other University of Auckland co-authors: Margaret Brimble
  • Wang, Y., Yang, S. H., Brimble, M. A., & Harris, P. W. R. (2020). Recent Progress in the Synthesis of Homogeneous Erythropoietin (EPO) Glycoforms. CHEMBIOCHEM10.1002/cbic.202000347
    Other University of Auckland co-authors: Margaret Brimble
  • Lu, B. L., Loomes, K. M., Hay, D. L., Harris, P. W. R., & Brimble, M. A. (2020). Synthesis of isotopically labelled αCGRP8-37 and its lipidated analogue. Journal of Labelled Compounds and Radiopharmaceuticals, 63 (7), 325-332. 10.1002/jlcr.3838
    URL: http://hdl.handle.net/2292/51580
    Other University of Auckland co-authors: Debbie Hay, Kerry Loomes, Margaret Brimble, Benjamin Lu
  • Kavianinia, I., Stubbing, L. A., Abbattista, M. R., Harris, P. W. R., Smaill, J. B., Patterson, A. V., & Brimble, M. A. (2020). Alanine scan-guided synthesis and biological evaluation of analogues of culicinin D, a potent anticancer peptaibol. Bioorganic & Medicinal Chemistry Letters, 30 (11)10.1016/j.bmcl.2020.127135
    Other University of Auckland co-authors: Louise Stubbing, Iman Kavianinia, Jeff Smaill, Margaret Brimble, Adam Patterson
  • Tong, J. T. W., Kavianinia, I., Ferguson, S. A., Cook, G. M., Harris, P. W. R., & Brimble, M. A. (2020). Synthesis of paenipeptin C' analogues employing solution-phase CLipPA chemistry. Organic & biomolecular chemistry10.1039/d0ob00950d
    Other University of Auckland co-authors: Margaret Brimble, Iman Kavianinia
  • Yim, V. V., Kavianinia, I., Cameron, A. J., Harris, P. W. R., & Brimble, M. A. (2020). Direct synthesis of cyclic lipopeptides using intramolecular native chemical ligation and thiol-ene CLipPA chemistry. Organic & biomolecular chemistry, 18 (15), 2838-2844. 10.1039/d0ob00203h
    Other University of Auckland co-authors: Margaret Brimble, Iman Kavianinia, Alan Cameron
  • Yang, S.-H., Hermant, Y. O. J., Harris, P. W. R., & Brimble, M. A. (2020). Replacement of the Acrid tert-Butylthiol and an Improved Isolation Protocol for Cysteine Lipidation on a Peptide or Amino Acid (CLipPA). EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2020 (8), 944-947. 10.1002/ejoc.201901696
    Other University of Auckland co-authors: Margaret Brimble, Sung Hyun Yang
  • Cameron, A. J., Davison, E. K., An, C., Stubbing, L. A., Dunbar, P. R., Harris, P. W. R., & Brimble, M. A. (2020). Synthesis and SAR Analysis of Lipovelutibols B and D and Their Lipid Analogues. The Journal of organic chemistry, 85 (3), 1401-1406. 10.1021/acs.joc.9b02348
    Other University of Auckland co-authors: Margaret Brimble, Alan Cameron, Louise Stubbing, Emma Davison, Rod Dunbar

Identifiers

Contact details

Primary office location

THOMAS BUILDING EXTENSION - Bldg 110N
Level 4, Room 4012
3A SYMONDS ST
AUCKLAND CENTRAL
AUCKLAND 1010
New Zealand

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