Chemical Biology

Past Projects

Novel Hydrazide Dendrimer as Transient Inter-cellular Linker

1/5

Three-dimensional (3D) tissue-engineered constructs with bio-mimicry cell-cell and cell-matrix interactions are useful in regenerative medicine. In cell-dense and matrix poor tissues of the internal organs, cells support one another via cell-cell interactions, supplemented by small amount of the extra-cellular matrices (ECM) secreted by the cellls. We're interested in connecting cells directly but transiently with polymeric materials to facilitate cell-cell interaction and aggregation. We propose that the linker consists of non-toxic low molecular-weight polyethyleneimine (PEI) backbone conjugated with multiple hydrazide groups that might aggregate cells in short periods of time by reacting the aldehyde handles on the chemically modified cell-surface glycoproteins. Should it be successful, the cells in the cellular aggregates should proliferate and mantain the cortical actin distribution of the 3D cell morphology while non-aggregated cells die after longer time of suspension culture. The aggregates should then lose distinguishable cell-cell boundaries and the ECM fibers become visible around cells while the polymeric materials disappear from the cell surfaces over time. The transient inter-cellular polymeric linker can be useful for forming 3D cellular and tissue constructs without bulk biomaterials or extensive network of engineered ECM for various applications.

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Collaborators:  

  • Professor Hanry Yu (Yong Loo Lin School of Medicine, NUS)

Selected Publications:

  • B. Nugraha, X. Hong, X. Mo, L. Tan, W. Zhang, P.-M. Chan, C. H. Kang, Y. Wang, L. T. Beng, W. Sung, D. Choudhury, J. M. Rubens, M. McMillian, J. Silva, S. Dallas, C.-H. Tan, Z. Yue, Hanry Yu, Galactosylated cellulosic sponge for multi-well drug safety testing, Biomaterials, 2011, 32, 6982–6994.

  • X. Mo, Q. Li, L. Wai Y. L., B. Zheng C. H. Kang, B. Nugraha, Z. Yue, R. R. Jia, H. X. Fu, D. Choudhury, T. Arooz, J. Yan, C. T. Lim, S. Shen, C.-H. Tan, Hanry Yu, Rapid construction of mechanically-confined multi-cellular structures using dendrimeric intercellular linker, Biomaterials, 2010, 31, 7455 – 7467.

  • D. Q. Zhao, Z.L. Yue, S. M. Ong, Y.C. Toh, Z.Y. Jiang, C.-H Tan, J.P. Chen and H. Yu, Novel hydrazide dendrimer as transient inter-cellular linker, Biomaterials, 2008, 29, 3693–3702.

  • S.M. Ong, L. He, N.T.T. Linh, Y.H. Tee, T. Arooz, G.P. Tang, C.H. Tan and Yu H. Transient inter-cellular polymeric linker. Biomaterials, 2007, 28, 3656–3667.

Design and Synthesis of Slow Hydrogen Sulfide Donors

2/5

Hydrogen sulfide (H2S) has recently emerged as an important biological gasomediator as a result of numerous insightful studies. The use of H2S releasing compounds has attracted much attention as they can exert crucial effects on a wide range of cellular signaling processes. Some of these effects are potentially exploitable in terms of anti-inflammatory and anti-tumor effects, as well as precise ion-channel regulation, cardiovascular protection and oxidation resistance. Chemical compounds with the ability to release H2S over a prolonged period of time have proved very useful in our understanding of the physiological and pathophysiological roles of this gas. We are the first to develop a slow-releasing hydrogen sulfide donor, GYY4137 that is shown to be effective both in vitro and in vivo. This drug is now sold in more that 30 chemical companies worldwide. Our interests revolve around the physiology and biochemistry of H2S, the effects ofH2S inhibitors or H2S donors in animal models of disease and focuses on the potential options for the therapeutic exploitation of H2S.

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Collaborators:

  • Professor Phillip Moore (Executive Director of NUS Graduate School of Integrative Sciences and Engineering)

  • Associate Prof. Jayaraman Sivaraman (Department of Biological Sciences, NUS)

  • Associate Prof. Brian Dymock (Department of Pharmacy, NUS)

  • Associate Prof. Deng Lihwen (Department of Biochemistry, NUS)

Selected Publications:

  • Z.-W. Lee, X.-Y. Teo, Evon Y.-W. Tay, C.-H. Tan, T. Hagen, P. K. Moore, L.-W. Deng, Utilizing hydrogen sulfide as a novel anti-cancer agent by targeting cancer glycolysis and pH imbalance, 2014, British Journal of Pharmacology, 2014, 171, 4322 – 4336.

  • Z. Liu, Y. Han, L. Li, H. Lu, X. Li, M. Shirhan, M. T. Peh, L. Xie, Y. Tang, S. Zhou, X. Wang, Q. Chen, W. Dai, C.-H. Tan, P. K. Moore, Y. Ji, The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E-/- knockout mice, British Journal of Pharmacology, 2013, 169, 1795–1809.

  • Z. W. Lee, J. Zhou, C.-S. Chen, Y. Zhao, C.-H. Tan, Ling Li, P. K. Moore, L.-W. Deng, The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo, PLoS ONE, 2011, 6, e21077.

  • L. Li, M. Whiteman, Y. Y. Guan, K. L. Neo, Y. Cheng, S. W. L, Y. Zhao, R. Baskar, C.-H. Tan and P. K. Moore, Characterisation of a novel, water soluble hydrogen sulfide releasing molecule (GYY4137): new insights into the biology of hydrogen sulphide, Circulation, 2008, 117, 2351–2360.

More about GYY4137:

GYY4137 was first synthesised by Ms Guan Yanyi, a MSc student in TCH Laboratory, on 28 Apr 2006. It was recorded by Ms Guan on page 137 of her fourth labbook. GYY4137 was one of a series of compounds designed and synthesised by Ms Guan and Prof Tan. They were subsequently sent to Prof Moore to be evaluated as a slow H2S releaser.

Novel 11C-Radiolabelling Methodologies

3/5

Clinicians today utilize a wide range of tools and information to help treatment, diagnosis and evaluation of a disease. One of such informative tools is positron emission tomography (PET), which can provide visualization and quantitative measurements of metabolic, biochemical and physiological function in vivo in real time using short-lived positron-emitting molecular probes (radiotracers). However, there are limited numbers of radioligands available for clinical studies or research to date due to the stringent criteria required of a radiotracer and the relatively complex preparation process of the radiotracer. We aim to develop a technological platform (through chemical methodology and instrumentation engineering) to advance radiolabeling efficiency and expedite the development of new or existing PET imaging probes. Specifically, a versatile [11C]CO2 fixation strategy based on guanidine bases would be developed to advance the [11C]CO2 labeling technologies, expanding the scope of molecules that can be radiolabeled and increasing the portfolio of radiotracers available for PET studies.

Collaborators:

  • Prof Christer Hallidin (Visiting Professor in Lee Kong Chian School of Medicine, NTU; Full Professor in Karolinska Institute)

  • Dr. Lim Yee Hwee (Institute of Chemical and Engineering Sciences, A*STAR)

  • Assistant Prof. Kang Yuejun (School of Chemical and Biomedical Engineering, NTU) 

Synthetic Water Channel for Desalination Membranes

4/5

Selected Publications:

  • ​M.-Y. Jin, Y. Liao, Y. Lin, C.-H. Tan, R. Wang, Development of Highly-Efficient ZIF-8@PDMS/PVDF Nanofibrous Composite Membrane for Phenol Removal in Aqueous-Aqueous Membrane Extractive Process, Journal of Membrane Science, 2018, 568, 121 - 133. 

  • Q. Li, X. Li, L. Ning, C.-H. Tan, Y. Mu, R. Wang, Hyperfast water transport through biomimetic nanochannels from peptide-attached (pR)-pillar[5]arene, Small, 2019, 15, 1804678.

  • Y. Yang, Y. Li, Q. Lin, Y.-N. Wang, C.-H. Tan, R. Wang, Rapid co-deposition of graphene oxide incorporated metal-phenolic network/piperazine followed by crosslinking for high flux nanofiltration membrane, Journal of Membrane Science, 2019, 588, 117203 - 117212. 

  • Y. Yang, Y. Li, K. Goh, C.-H. Tan, R. Wang, Liposomes-assisted fabrication of high performance thin film composite nanofiltration membrane, Journal of Membrane Science, 2021, accepted. 

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Synthetic membranes can be formed, by incorporating artificial water channels, with nanotubular structures. Compared to the membranes using aquaporins, the synthetic water channels have several potential advantages, such as high stability, controllability, lower cost and the scalability of their production and the ability to be immobilized in membrane-like supports in a scalable manner.

Collaborator:

  • Prof Wang Rong (Chair, School of Civil and Environmental Engineering, NTU)

Development of Next-generation Antibiofilm Drugs

5/5

Bacterial pathogens coordinate social behaviors such as swarming motility and biofilm formation via cell-to-cell communications (also called quorum sensing) and c-di-GMP signaling. Once formed, biofilms are extremely difficult to eradicate. Targeting these regulatory mechanisms will enable us to develop next generation antibiofilm drugs.

Collaborator:

  • Dr Thomas Nielsen, University of Copenhagen

  • Prof Michael Givskov SCELSE (Singapore Centre on Environmental Life Sciences Engineering), NTU

  • Asst Prof Yang Liang SCELSE, NTU

Selected Publications: 

  • J. Fong, M. Yuan, T. H. Jakobsen, D. Santos, M. M. Salido, S. L. Chua, L. Yang, C.-H. Tan, T. E. Nielsen, M. Givsgov, Disulfide bond-containing ajoene analogs as novel quorum sensing inhibitors of Pseudomonas aeruginosa, 2017, Journal of Medicinal Chemistry, 2017, 60, 215 - 227. 

  • Y. Liang, D. Zeng, X. Huang, L. Chan, C. Mei, P. Feng, C.-H. Tan, T. Chen, Cancer-targeted Design of Bioresponsive Prodrug with Enhanced Cellular Uptake for Precise Cancer Therapy, Drug Delivery, 2018, 25, 1350-1361. 

  • M. Yuan, S. L. Chua, Y. Liu, D. I. Drautz-Moses, J. K. H. Yam, T. T. Aung, R. W. Beuerman, M. M. S. Salido, S. C. Scjister, C.-H. Tan, M. Givskov, K. Yang, T. E. Nielsen, Repurposing the anti-cancer drug cisplatin as an effective Pseudomonas aeruginosa infected control agent, Beilstein Journal of Organic Chemistry, 2018, 14, 3059 - 3069. 

  • J. Fong, K. T. Mortensen, A. Nørskov, K. Qvortrup, L. Yang, C.-H. Tan, T. E. Nielsen, M. Givskov, Itaconimides as Novel Quorum Sensing Inhibitors of Pseudomonas areuginosa, Frontiers in Cellular and Infection Microbiology,  2019, 8, 443.