Dr Dominic Alonzi

MBiochem; DPhil; FHEA

I read Molecular and Cellular Biochemistry at Corpus Christi, Oxford before reading for a DPhil at Linacre College with Dr Terry Butters and Prof Raymond Dwek, CBE, FRS at the Oxford Glycobiology Institute, Department of Biochemistry.

I lecture in Glycobiology to Biochemistry undergraduates and teach a variety of cell biology and biological chemistry topics to biochemistry undergraduates via tutorials: enzymes, drug design, virology, protein structure and function, cell membranes and metabolism.

My research involves working in the field of glycobiology. Glycobiology has made major contributions to understanding concepts in protein folding, immunology and virology, laying the foundations for applying glycobiology to the development of novel strategies for therapeutics. Inhibitors of the glycosylation pathway can perturb glycan dependent protein folding in the ER with clinically relevant broad-spectrum antiviral properties, with a class of small molecule inhibitors known as iminosugars leading the research in this field. I examine how these small molecule inhibitors can have an affect on a number of cellular targets to enhance and elucidate their therapeutic potential and multiple mechanisms of action.

1. Glucosylated free oligosaccharides are biomarkers of endoplasmic reticulum alpha-glucosidase inhibition. D.S. Alonzi, D.C. Neville, R.H. Lachmann, R.A. Dwek and T.D. Butters (2008) Biochem. J., 409, 571-580.

2. Therapeutic targets for inhibitors of glycosylation. D.S. Alonzi and T.D. Butters (2011) Chimia, 65, 35-39.

3. Urinary glycan markers for disease. D.S. Alonzi, Y.-H. Su and T.D. Butters (2011) Biochem. Soc. Trans, 39, 393-398.

4. Structural and mechanistic insight into N-glycan processing by endo-α-mannosidase. A.J Thompson, R.J. Williams, Z. Hakki, D.S. Alonzi, T. Wennekes, T.M. Gloster, K. Songsrirote, J.E. Thomas-Oates, T.M. Wrodnigg, J. Spreitz, A.E. Stütz, T.D. Butters, S.J. Williams, G.J. Davies. Proc Natl Acad Sci U S A. (2012) 109(3):781-6.

5. Glycoprotein misfolding in the endoplasmic reticulum: identification of released oligosaccharides reveals a second ER-associated degradation pathway for Golgi retrieved proteins. D. S. Alonzi, N. V. Kukushkin, S. A. Allman, Z. Hakki, S. J. Williams, L. Pierce, R. A. Dwek and T. D. Butters. Cellular and Molecular Life Sciences (2013) Cell Mol Life Sci. Aug;70(15):2799-814.

6. Structures of mammalian ER α-glucosidase II capture the binding modes of broadspectrum iminosugar antivirals. A. T. Caputo, D. S. Alonzi, L. Marti, I. B. Reca, J. L. Kiappes, W, B. Struwe, A. Cross, S. Basu, E. D. Lowe, B. Darlot, A. Santino, P. Roversi, N. Zitzmann. Proc Natl Acad Sci U S A. (2016) Aug 9;113(32)

7. Iminosugar antivirals: the therapeutic sweet spot. D. S. Alonzi, K.A Scott, R. A. Dwek, N Zitzmann. Biochem Soc Trans. (2017) Apr 15;45(2):571-582

8. Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint P. Roversi, L. Marti, A. T. Caputo, D.S. Alonzi, J.C. Hill, K. C. Dent, A. Kumar, M. D. Levasseur, A. Lia, T. Waksman, S. Basu, Y. Soto Albrecht, K. Qian, J. P. McIvor, Lipp, D. Siliqi, S. Vasiljević, S. Mohammed, P. Lukacik, M. A.Walsh, A. Santino, N. Zitzmann. Proc Natl Acad Sci U S A. (2017) Aug 8;114(32):8544-8549

9. Targeting Endoplasmic Reticulum α-Glucosidase I with a Single-Dose Iminosugar Treatment Protects against Lethal Influenza and Dengue Virus Infections. K.L. Warfield, D.S. Alonzi, J.C. Hill, A. T. Caputo, P. Roversi, J.L. Kiappes, N. Sheets, M. Duchars, R.A. Dwek, J. Biggins, D.

Barnard, S. Shresta, A.M. Treston, N. Zitzmann. J Med Chem. (2020) Apr 23;63(8):4205-4214.

10. Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host glycosylation target. L.F. Sobala, P. Z. Fernandes, Z. Hakki, A. J. Thompson, J. D. Howe, M. Hill, N. Zitzmann, S. Davies, Z. Stamataki, T.D. Butters, D.S. Alonzi, S.J. Williams, G.J. Davies. Proc Natl Acad Sci U S A. (2020) Nov 24;117(47):29595-29601.

11. Assessing Antigen Structural Integrity through Glycosylation Analysis of the SARS-CoV-2 Viral Spike. J. Brun, S. Vasiljevic, B Gangadharan, M. Hensen, A. V. Chandran, M. L. Hill, J.L. Kiappes, R. A. Dwek, D S. Alonzi, W. B. Struwe, N. Zitzmann ACS Cent. Sci. (202) Apr, 7, 586−593