Dr Ashleigh Paparella
School of Medical Sciences
Faculty of Medicine and Health
2023 - current: Lecturer, School of Medical Sciences, University of Sydney
The transition state structure of an enzyme-catalysed reaction is high energy, unstable structure which is positioned between the chemical structures of the reactants and products. Enzymes function by lowering the energy barrier required to form the transition state, thereby increasing the rate of reaction. Knowledge of the transition state structure is critical to understanding the mechanisms of enzymes and importantly can be exploited to generate new drugs. Drugs that mimic the transition state of an enzyme catalysed reaction are known as transition state analogues and are tight binding enzyme inhibitors.
My research involves studying the transition state features of a class of enzymes known as glycosyltransferases. Glycosyltransferases catalyse the transfer of a sugar from a donor substrate to an acceptor which can include sugars, proteins and lipids. I am particularly interested in studying the transition states of glycosyltransferases that are involved in the synthesis and modification of peptidoglycan and applying this knowledge to develop new antibiotics.
2022 - Dennis Shields Award for Postdoctoral Research Excellence, Albert Einstein College of Medicine
2019 - Postdoctoral Service Award, Albert Einstein College of Medicine
| Project title | Research student |
|---|---|
| Development of the First Two-Partner Secretion System Inhibitors | Alfred HARTOJO |
Publications
Journals
- Paparella, A., Cahill, S., Aboulache, B., Schramm, V. (2022). Clostridioides difficile TcdB Toxin Glucosylates Rho GTPase by an SNi Mechanism and Ion Pair Transition State. ACS Chemical Biology, 17(9), 2507-2518. [More Information]
- Paparella, A., Aboulache, B., Harijan, R., Potts, K., Tyler, P., Schramm, V. (2021). Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues. Nature Communications, 12(1), 6285. [More Information]
- Hayes, A., Satiaputra, J., Sternicki, L., Paparella, A., Feng, Z., Lee, K., Blanco-Rodriguez, B., Tieu, W., Eijkelkamp, B., Shearwin, K., et al (2020). Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase. Antibiotics, 9(4), 165. [More Information]
2022
- Paparella, A., Cahill, S., Aboulache, B., Schramm, V. (2022). Clostridioides difficile TcdB Toxin Glucosylates Rho GTPase by an SNi Mechanism and Ion Pair Transition State. ACS Chemical Biology, 17(9), 2507-2518. [More Information]
2021
- Paparella, A., Aboulache, B., Harijan, R., Potts, K., Tyler, P., Schramm, V. (2021). Inhibition of Clostridium difficile TcdA and TcdB toxins with transition state analogues. Nature Communications, 12(1), 6285. [More Information]
2020
- Hayes, A., Satiaputra, J., Sternicki, L., Paparella, A., Feng, Z., Lee, K., Blanco-Rodriguez, B., Tieu, W., Eijkelkamp, B., Shearwin, K., et al (2020). Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase. Antibiotics, 9(4), 165. [More Information]
2018
- Paparella, A., Lee, K., Hayes, A., Feng, J., Feng, Z., Cini, D., Deshmukh, S., Booker, G., Wilce, M., Polyak, S., et al (2018). Halogenation of Biotin Protein Ligase Inhibitors Improves Whole Cell Activity against Staphylococcus aureus. ACS Infectious Diseases, 4(2), 175-184. [More Information]
2016
- Feng, J., Paparella, A., Booker, G., Polyak, S., Abell, A. (2016). Biotin Protein Ligase Is a Target for New Antibacterials. Antibiotics, 5(3), 26. [More Information]
- Feng, J., Paparella, A., Tieu, W., Heim, D., Clark, S., Hayes, A., Booker, G., Polyak, S., Abell, A. (2016). New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase. ACS Medicinal Chemistry Letters, 7(12), 1068-1072. [More Information]
2015
- Tieu, W., Polyak, S., Paparella, A., Yap, M., Soares da Costa, T., Ng, B., Wang, G., Lumb, R., Bell, J., Turnidge, J., et al (2015). Improved synthesis of biotinol-5′-AMP: Implications for antibacterial discovery. ACS Medicinal Chemistry Letters, 6(2), 216-220. [More Information]
Selected Grants
2024
- 2024 EMCR Scheme, Paparella A, Centre for Drug Discovery Innovation/EMCR Seed Funding
- SABA Program Funding 2024, Paparella A, Centre for Drug Discovery Innovation/SABA Discovery Funding
2023
- FMH Start-up Scheme, Paparella A, Faculty of Medicine and Health/New Academic Staff Funding