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1. The Influence of Substitution on Thiol-Induced Oxanorbornadiene Fragmentation

Author

De Pascalis, Lucrezia, Yau, Mei-Kwan, Svatunek, Dennis, Tan, Zhuoting, Tekkam, Srinivas, Houk, KN, and Finn, MG

Subjects
Organic Chemistry, Chemical Sciences, Cycloaddition Reaction, Electrons, Furans, Molecular Structure, Sulfhydryl Compounds, Chemical sciences
Abstract

Oxanorbornadienes (ONDs) undergo facile Michael addition with thiols and then fragment by a retro-Diels-Alder (rDA) reaction, a unique two-step sequence among electrophilic cleavable linkages. The rDA reaction rate was explored as a function of the furan structure, with substituents at the 2- and 5-positions found to be the most influential and the fragmentation rate to be inversely correlated with electron-withdrawing ability. Density functional theory calculations provided an excellent correlation with the experimentally measured OND rDA rates.

Published
2021

5. Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion

Author

Duszyc, Kinga, primary, Gomez, Guillermo A., additional, Lagendijk, Anne K., additional, Yau, Mei-Kwan, additional, Nanavati, Bageshri Naimish, additional, Gliddon, Briony L., additional, Hall, Thomas E., additional, Verma, Suzie, additional, Hogan, Benjamin M., additional, Pitson, Stuart M., additional, Fairlie, David P., additional, Parton, Robert G., additional, and Yap, Alpha S., additional

Published
2021
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7. A unified view of neighbour cell engagement during apoptotic cell extrusion

Author

Duszyc, Kinga, primary, Gomez, Guillermo A., additional, Lagendijk, Anne K., additional, Yau, Mei-Kwan, additional, Gliddon, Briony L., additional, Hall, Thomas E., additional, Verma, Suzie, additional, Hogan, Benjamin M., additional, Pitson, Stuart M., additional, Fairlie, David P., additional, Parton, Robert G., additional, and Yap, Alpha S., additional

Published
2020
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9. Transport of Molecular Cargo by Interaction with Virus‐Like Particle RNA.

Author

Das, Soumen, Yau, Mei‐Kwan, Noble, Jeffery, De Pascalis, Lucrezia, and Finn, M. G.

Subjects
*VIRUS-like particles, *MOLECULAR interactions, *PARTICLE interactions, *RNA, *MOLECULES, *POLYETHYLENE glycol, *OLIGOPEPTIDES
Abstract

Virus‐like particles (VLPs) derived from Leviviridae virions contain substantial amounts of cellular and plasmid‐derived RNA. This encapsidated polynucleotide serves as a reservoir for the efficient binding of the intercalating dye thiazole orange (TO). Polyethylene glycol (PEG) molecules and oligopeptides of varying length, end‐functionalized with TO, were loaded into VLPs up to approximately 50 % of the mass of the capsid protein (hundreds to thousands of cargo molecules per particle, depending on size). The kinetics of TO–PEG binding included a significant entropic cost for the reptation of long chains through the capsid pores. Cargo molecules were released over periods of 20–120 hours following simple reversible first‐order kinetics in most cases. These observations define a simple general method for the noncovalent packaging, and subsequent release, of functional molecules inside nucleoprotein nanocages in a manner independent of modifications to the capsid protein. [ABSTRACT FROM AUTHOR]

Published
2022
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13. Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a

Author

Lohman, Rink-Jan, primary, Hamidon, Johan K., additional, Reid, Robert C., additional, Rowley, Jessica A., additional, Yau, Mei-Kwan, additional, Halili, Maria A., additional, Nielsen, Daniel S., additional, Lim, Junxian, additional, Wu, Kai-Chen, additional, Loh, Zhixuan, additional, Do, Anh, additional, Suen, Jacky Y., additional, Iyer, Abishek, additional, and Fairlie, David P., additional

Published
2017
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15. Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China

Author

Tian, Huai-Yu, Huang, Shan-Qian, Zhou, Sen, Bi, Peng, Yang, Zhicong, Li, Xiu-Jun, Chen, Lifan, Cazelles, Bernard, Yang, Jing, Luo, Lei, Jing, Qinlong, Yuan, Wenping, Pei, Yao, Sun, Zhe, Yue, Tianxiang, Yau, Mei-Kwan, Liu, Qiyong, Wang, Ming, Tong, Shilu, Brownstein, John, Xu, Bing, Tian, Huai-Yu, Huang, Shan-Qian, Zhou, Sen, Bi, Peng, Yang, Zhicong, Li, Xiu-Jun, Chen, Lifan, Cazelles, Bernard, Yang, Jing, Luo, Lei, Jing, Qinlong, Yuan, Wenping, Pei, Yao, Sun, Zhe, Yue, Tianxiang, Yau, Mei-Kwan, Liu, Qiyong, Wang, Ming, Tong, Shilu, Brownstein, John, and Xu, Bing

Abstract

Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment–mosquito–urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface area covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world.

Published
2016

16. Potent Small Agonists of Protease Activated Receptor 2

Author

Yau, Mei Kwan, Suen, Jacky Y., Xu, Weijun, Lim, Junxian, Liu, Ligong, Adams, Mark N., He, Yaowu, Hooper, John D., Reid, Robert C., Fairlie, David P., Yau, Mei Kwan, Suen, Jacky Y., Xu, Weijun, Lim, Junxian, Liu, Ligong, Adams, Mark N., He, Yaowu, Hooper, John D., Reid, Robert C., and Fairlie, David P.

Abstract

Many proteases cut the PAR2 N-terminus resulting in conformational changes that activate cells. Synthetic peptides corresponding to newly exposed N-terminal sequences of PAR2 also activate the receptor at micromolar concentrations. PAR2-selective small molecules reported here induce PAR2-mediated intracellular calcium signaling at nanomolar concentrations (EC50 = 15-100 nM, iCa2+, CHO-hPAR2 cells). These are the most potent and efficient small molecule ligands to activate PAR2-mediated calcium release and chemotaxis, including for human breast and prostate cancer cells.

Published
2016

17. PAR2 Modulators Derived from GB88

Author

Yau, Mei-Kwan, primary, Liu, Ligong, additional, Suen, Jacky Y., additional, Lim, Junxian, additional, Lohman, Rink-Jan, additional, Jiang, Yuhong, additional, Cotterell, Adam J., additional, Barry, Grant D., additional, Mak, Jeffrey Y. W., additional, Vesey, David A., additional, Reid, Robert C., additional, and Fairlie, David P., additional

Published
2016
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18. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

Author

Seow, Vernon, primary, Lim, Junxian, additional, Cotterell, Adam J., additional, Yau, Mei-Kwan, additional, Xu, Weijun, additional, Lohman, Rink-Jan, additional, Kok, W. Mei, additional, Stoermer, Martin J., additional, Sweet, Matthew J., additional, Reid, Robert C., additional, Suen, Jacky Y., additional, and Fairlie, David P., additional

Published
2016
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20. Potent Small Agonists of Protease Activated Receptor 2

Author

Yau, Mei-Kwan, primary, Suen, Jacky Y., additional, Xu, Weijun, additional, Lim, Junxian, additional, Liu, Ligong, additional, Adams, Mark N., additional, He, Yaowu, additional, Hooper, John D., additional, Reid, Robert C., additional, and Fairlie, David P., additional

Published
2015
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23. Downsizing Proteins Without Losing Potency or Function

Author

Yau, Mei-Kwan, additional, Hamidon, Johan K., additional, Singh, Ranee, additional, Lim, Junxian, additional, Suen, Jacky Y., additional, Rowley, Jessica A., additional, Lohman, Rink-Jan, additional, Stoermer, Martin J., additional, Iyer, Abishek, additional, and Reid, Robert C., additional

Published
2015
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26. Downsizing a human inflammatory protein to a small molecule with equal potency and functionality

Author

Reid, Robert C., primary, Yau, Mei-Kwan, additional, Singh, Ranee, additional, Hamidon, Johan K., additional, Reed, Anthony N., additional, Chu, Peifei, additional, Suen, Jacky Y., additional, Stoermer, Martin J., additional, Blakeney, Jade S., additional, Lim, Junxian, additional, Faber, Jonathan M., additional, and Fairlie, David P., additional

Published
2013
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33. Potent Heterocyclic Ligandsfor Human Complement C3aReceptor.

Author

Reid, Robert C., Yau, Mei-Kwan, Singh, Ranee, Hamidon, Johan K., Lim, Junxian, Stoermer, Martin J., and Fairlie, David P.

Subjects
*LIGANDS (Biochemistry), *G protein coupled receptors, *INFLAMMATION, *METABOLIC disorders, *IMMUNOLOGIC diseases, *RECEPTOR-ligand complexes
Abstract

TheG-protein coupled receptor (C3aR) for human inflammatory proteincomplement C3a is an important component of immune, inflammatory,and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist(IC50μM), was transformed here into potent agonists(EC50nM) of human macrophages (Ca2+releasein HMDM) by incorporating aromatic heterocycles. Antagonists werealso identified. A linear correlation between binding affinity forC3aR and calculated hydrogen-bond interaction energy of the heteroatomindicated that its hydrogen-bonding capacity influenced ligand affinityand function mediated by C3aR. Hydrogen-bond accepting heterocycles(e.g., imidazole) conferred the highest affinity and agonist potency(e.g., 21, EC5024 nM, Ca2+, HMDM)with comparable efficacy and immunostimulatory activity as that ofC3a in activating human macrophages (Ca2+, IL1β,TNFα, CCL3). These potent and selective modulators of C3aR,inactivated by a C3aR antagonist, are stable C3a surrogates for interrogatingroles for C3aR in physiology and disease. [ABSTRACT FROM AUTHOR]

Published
2014
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34. Efficient chemical synthesis of human complement protein C3a.

Author

GhassemianThese authors contributed equally., Artin, Wang, Ching-I Anderson, Yau, Mei-Kwan, Reid, Robert C., Lewis, Richard J., Fairlie, David P., Alewood, Paul F., and Durek, Thomas

Subjects
CRYSTAL structure, POLYTYPIC transformations, CRYSTALLOGRAPHY, CONDENSED matter physics, CHEMICAL synthesis
Abstract

We report the total chemical synthesis of human C3a by one-pot native chemical ligation of three unprotected peptide segments, followed by efficient in vitro folding that yielded the anaphylatoxin C3a in high yield and excellent purity. Synthetic C3a was fully active and its crystal structure at 2.1 Å resolution showed 3 helices and a C-terminal turn motif. [ABSTRACT FROM AUTHOR]

Published
2013
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36. MODULATORS OF PROTEASE ACTIVATED RECEPTORS

Author

Fairlie David Paul, Liu Ligong, Yau Mei-kwan, Jacky Suen, Reid Robert, Lohman Rink-jan, Iyer Abishek Venkatasubramanian, Lim Junxian, and Brown Lindsay Charles

37. Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion

Author

David P. Fairlie, Briony L. Gliddon, Suzie Verma, Bageshri Naimish Nanavati, Benjamin M. Hogan, Alpha S. Yap, Thomas E. Hall, Guillermo A. Gomez, Mei-Kwan Yau, Stuart M. Pitson, Anne K. Lagendijk, Robert G. Parton, Kinga Duszyc, Duszyc, Kinga, Gomez, Guillermo A, Lagendijk, Anne K, Yau, Mei Kwan, Nanavati, Bageshri Naimish, Gliddon, Briony L, Hall, Thomas E, Verma, Suzie, Hogan, Benjamin M, Pitson, Stuart M, Fairlie, David P, Parton, Robert G, and Yap, Alpha S

Subjects
0301 basic medicine, RHOA, Cell, Apoptosis, Mechanotransduction, Cellular, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Sphingosine, medicine, Animals, Mechanotransduction, Zebrafish, mechanotransduction, biology, Epidermis (botany), RhoA, Epithelial Cells, biology.organism_classification, Cadherins, Epithelium, Cell biology, apoptotic elimination, 030104 developmental biology, medicine.anatomical_structure, epithelial apoptosis, apical extrusion, biology.protein, Lysophospholipids, General Agricultural and Biological Sciences, rhoA GTP-Binding Protein, 030217 neurology & neurosurgery, Cytokinesis
Abstract

Epithelia must eliminate apoptotic cells to preserve tissue barriers and prevent inflammation.1 Several different mechanisms exist for apoptotic clearance, including efferocytosis2,3 and apical extrusion.4,5 We found that extrusion was the first-line response to apoptosis in cultured monolayers and in zebrafish epidermis. During extrusion, the apoptotic cell elicited active lamellipodial protrusions and assembly of a contractile extrusion ring in its neighbors. Depleting E-cadherin compromised both the contractile ring and extrusion, implying that a cadherin-dependent pathway allows apoptotic cells to engage their neighbors for extrusion. We identify RhoA as the cadherin-dependent signal in the neighbor cells and show that it is activated in response to contractile tension from the apoptotic cell. This mechanical stimulus is conveyed by a myosin-VI-dependent mechanotransduction pathway that is necessary both for extrusion and to preserve the epithelial barrier when apoptosis was stimulated. Earlier studies suggested that release of sphingosine-1-phosphate (S1P) from apoptotic cells might define where RhoA was activated. However, we found that, although S1P is necessary for extrusion, its contribution does not require a localized source of S1P in the epithelium. We therefore propose a unified view of how RhoA is stimulated to engage neighbor cells for apoptotic extrusion. Here, tension-sensitive mechanotransduction is the proximate mechanism that activates RhoA specifically in the immediate neighbors of apoptotic cells, but this also must be primed by S1P in the tissue environment. Together, these elements provide a coincidence detection system that confers robustness on the extrusion response. Refereed/Peer-reviewed

Published
2020

38. Patent Issued for Modulations of Protease Activated Receptors

Subjects
Patents, Proteases -- Intellectual property, Patent/copyright issue, Biotechnology industry, Pharmaceuticals and cosmetics industries, University of Queensland -- Intellectual property
Abstract

By a News Reporter-Staff News Editor at Biotech Week -- A patent by the inventors Fairlie, David Paul (Brisbane, AU); Liu, Ligong (Brisbane, AU); Yau, Mei Kwan (Brisbane, AU); Suen, [...]

Published
2015

39. Patent Issued for Modulations of Protease Activated Receptors

Subjects
Proteases -- Intellectual property, Patents, Patent/copyright issue, Biotechnology industry, Pharmaceuticals and cosmetics industries, University of Queensland -- Intellectual property
Abstract

By a News Reporter-Staff News Editor at Biotech Week -- A patent by the inventors Fairlie, David Paul (Brisbane, AU); Liu, Ligong (Brisbane, AU); Yau, Mei Kwan (Brisbane, AU); Suen, [...]

Published
2014

40. Patent Issued for Modulators of Protease Activated Receptors (USPTO 9701711)

Subjects
Physical fitness, Patents, Proteases -- Intellectual property, Patent/copyright issue, Health, University of Queensland -- Intellectual property
Abstract

2017 JUL 29 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a [...]

Published
2017

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