研究員

wcheng
02-27871262

EDUCATION AND POSITIONS HELD:

• B.S., Chemistry, National Cheng-Kung University Taiwan, 1991
• M.S., Chemistry National Tsing-Hua University Taiwan, 1993
• Ph.D., Chemistry, University of California, Davis CA, USA, 1997-2002
• Postdoctoral Fellow, the Scripps Research Institute, USA, 2002-2004
• Assistant Professor, Genomics Research Center, Academia Sinica, Taiwan, 2004-2010
• Associate Professor, Genomics Research Center, Academia Sinica, Taiwan, 2010-2023
• Professor, Genomics Research Center, Academia Sinica, Taiwan, 2023-present

HONORS:

• Skaggs Postdoctoral Fellowship, 2002-2004
• The distinguished lectureship award (Natural products synthesis), the CSJ (Chemical Society of Japan) Asian International Symposium, Japan, 2007

RESEARCH INTERESTS:

The major research efforts of this group are directed toward the development of new synthetic strategies for biologically interesting natural products and heterocyclics. To understand the relationships between small molecules and biological systems, combinatorial approaches are applied in our diverse molecule library synthesis (core diversity, substituent diversity, and configuration diversity) with the assistance of automated or semi-automated equipment.

• Organic Chemistry and Chemical Biology
• Development of new synthetic methodology
• Natural product and natural product-like molecule synthesis
• Synthesis of biologically interesting molecule libraries
• Development of new high-throughput library synthesis
• Combinatorial approach towards the synthesis of natural product-like or novel heterocyclic molecule libraries
• Study of the cell wall transglycosylase as a potential antibacterial target
• Lead discovery of cell wall synthesis enzymes in mycobacterium
• Novel chemical probe synthesis and application
• Synthesis of chemical chaperones towards lysosomal storage disease associated enzymes
• Synthesis of novel five- and six-membered iminosugars

我的研究興趣包括各式生化活性產物的全合成、新的合成方法學、組合式化學、固相有機合成、化學生物學，以及新藥開發等。

同時也根據理論設計與組合式化學的合成方法，將包括雜環、非天然之氨基酸 (胜肽)、lysophosphatidic acid衍生物以及iminocyclotals等之新穎的小分子設計並合成為抑制劑或抗頡劑(agonists)，以與疾病有關的酵素或受體 (receptors)為標的，研究其結構與活性之間的關係(SARs)。

由於近來在小分子組合式化學的研究日趨活絡，因此固相有機合成(SPOS)方面的應用與研究也受到高度關注。在此領域裡，我們的興趣在於新功能化樹 脂開發、linker開發(尤其是traceless linkers)、化學轉換、SPOS裂解策略，以及利用新方法來更有效率地建置小分子資料庫以供生化篩選使用。

SELECTED PUBLICATIONS:

• Lin Hung-Yi, Chang Shih-Ying, Teng Hsuan-Hsuan, Wu Hsi-Ju, Li Huang-Yi, Cheng Chia-Chun, Chuang Chih-Kuang, Lin Hsiang-Yu, Lin Shuan-Pei, Cheng Wei-Chieh, 2023, “Discovery of small-molecule protein stabilizers toward exogenous alpha-l-iduronidase to reduce the accumulated heparan sulfate in mucopolysaccharidosis type I cells”, European Journal of Medicinal Chemistry, 247, 115005. (SCIE)
• Li Huang-Yi, Lee Ni-Chung, Chiu Yu-Ting, Chang Yu-Wen, Lin Chu-Chung, Chou Cheng-Li, Chien Yin-Hsiu, Hwu Wuh-Liang, Cheng Wei-Chieh, 2023, “Harnessing polyhydroxylated pyrrolidines as a stabilizer of acid alpha-glucosidase (GAA) to enhance the efficacy of enzyme replacement therapy in Pompe disease”, BIOORGANIC & MEDICINAL CHEMISTRY, 78, 117129. (SCIE)
• Chen Wei-An, Chen Yu-Hsin, Hsieh Chiao-Yun, Hung Pi-Fang, Chen Chiao-Wen, Chen Chien-Hung, Lin Jung-Lee, Cheng Ting-Jen R., Hsu Tsui-Ling, Wu Ying-Ta, Shen Chia-Ning, Cheng Wei-Chieh, 2022, “Harnessing natural-product-inspired combinatorial chemistry and computation-guided synthesis to develop <i>N</i>-glycan modulators as anticancer agents”, Chemical Science, 13, 6233-6243. (SCIE)
• Cheng WC, Wang JH, Yun WY, Li HY, Hu JM, 2017, “Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease.”, European journal of medicinal chemistry, 126, 1-6. (SCIE)
• Cheng WC, Wang JH, Li HY, Lu SJ, Hu JM, Yun WY, Chiu CH, Yang WB, Chien YH, Hwu WL, 2016, “Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency.”, European journal of medicinal chemistry, 123, 14-20. (SCIE)
• Lin CK, Hou CC, Guo YY, Cheng WC, 2016, “Design and Synthesis of Orthogonally Protected d- and l-beta-Hydroxyenduracididines from d-lyxono-1,4-Lactone.”, Organic letters, 18(20), 5216-5219. (SCIE)
• Chen KT, Chen PT, Lin CK, Huang LY, Hu CM, Chang YF, Hsu HT, Cheng TJ, Wu YT, Cheng WC, 2016, “Structural Investigation of Park's Nucleotide on Bacterial Translocase MraY: Discovery of Unexpected MraY Inhibitors.”, Scientific reports, 6, 31579. (SCIE)
• Chen PT, Lin CK, Tsai CJ, Huang DY, Nien FY, Lin WW, Cheng WC, 2015, “Expeditious Synthesis of Enantiopure, Orthogonally Protected Bis-alpha-Amino Acids (OPBAAs) and their Use in a Study of Nod1 Stimulation.”, Chemistry-An Asian Journal, 10(2), 474-482. (SCIE)
• Cheng WC, Guo CW, Lin CK, Jiang YR, 2015, “Synthesis and Inhibition Study of Bicyclic Iminosugar-​Based Alkaloids, Scaffolds, and Libraries towards Glucosidase”, Israel Journal of Chemistry, 55(3-4), 403-411. (SCIE)
• Chen KT, Huang DY, Chiu CH, Lin WW, Liang PH, Cheng WC, 2015, “Synthesis of Diverse N-Substituted Muramyl Dipeptide Derivatives and Their Use in a Study of Human NOD2 Stimulation Activity.”, Chemistry-A European Journal, 21(34), 11984-11988. (SCIE)
• Cheng TJ, Chan TH, Tsou EL, Chang SY, Yun WY, Yang PJ, Wu YT, Cheng WC, 2013, “From Natural Product-Inspired Pyrrolidine Scaffolds to the Development of New Human Golgi alpha-Mannosidase II Inhibitors.”, Chemistry-An Asian Journal, 8(11), 2600-2604. (SCIE)
• Cheng WC, Weng CY, Yun WY, Chang SY, Lin YC, Tsai FJ, Huang FY, Chen YR, 2013, “Rapid modifications of N-substitution in iminosugars: development of new beta-glucocerebrosidase inhibitors and pharmacological chaperones for Gaucher disease.”, Bioorganic & medicinal chemistry, 21(17), 5021-5028. (SCIE)
• Chen KT, Kuan YC, Fu WC, Liang PH, Cheng TJ, Wong CH, Cheng WC, 2013, “Rapid preparation of mycobacterium N-glycolyl Lipid I and Lipid II derivatives: a biocatalytic approach.”, Chemistry-a European Journal, 19(3), 834-838. (SCIE)
• Huang CY, Shih HW, Lin LY, Tien YW, Cheng TJ, Cheng WC, Wong CH, Ma C, 2012, “Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism.”, Proceedings of the National Academy of Sciences of the United States of America, 109(17), 6496-6501. (SCIE)
• Shih HW, Chang YF, Li WJ, Meng FC, Huang CY, Ma C, Cheng TJ, Wong CH, Cheng WC, 2012, “Effect of the Peptide Moiety of Lipid II on Bacterial Transglycosylase.”, Angewandte Chemie-International Edition, 51(40), 10123-10126. (SCIE)
• Shih HW, Chen KT, Cheng TJ, Wong CH, Cheng WC, 2011, “A New Synthetic Approach toward Bacterial Transglycosylase Substrates, Lipid II and Lipid IV.”, Org. Lett., 13(17), 4600-4603. (SCIE)
• Chang YF, Guo CW, Chan TH, Pan YW, Tsou EL, Cheng WC, 2011, “Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids.”, Molecular diversity, 15(1), 203-214. (SCIE)
• Meng FC, Chen KT, Huang LY, Shih HW, Chang HH, Nien FY, Liang PH, Cheng TJ, Wong CH, Cheng WC, 2011, “Total Synthesis of Polyprenyl N-Glycolyl Lipid II as a Mycobacterial Transglycosylase Substrate.”, Org. Lett., 13(19), 5306-5309. (SCIE)
• Tin-Hao Chan, Yi-Fan Chang, Jung-Jung Hsu, and Wei-Chieh Cheng, 2010, “Straightforward Synthesis of Diverse 1-Deoxyazapyranosides via Stereocontrolled Nucleophilic Additons to Six-Membered Cyclic Nitrones”, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2010(59), 5555-5559. (SCIE)
• Chen-Yu Liu, Chih-Wei Guo, Yi-Fan Chang, Jen-Tsung Wang, Hao-Wei Shih, Yu-Fang Hsu, Chia-Wei Chen, Shao-Kang Chen, Yen-Chih Wang, Ting-Jen R. Cheng, Che Ma, Chi-Huey Wong, Jim-Min Fang* and Wei-Chieh Cheng*, 2010, “Synthesis and Evaluation of a New Fluorescent Transglycosylase Substrate: Lipid II-Based Molecule Possessing a Dansyl-C20 Polyprenyl Moiety”, Org. Lett., 12(7), 1608-1611.. (SCIE)
• Shih HW, Chen KT, Chen SK, Huang CY, Cheng TJ, Ma C, Wong CH, Cheng WC, 2010, “Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors.”, Organic & biomolecular chemistry, 8(11), 2586-2593. (SCIE)
• Sung, M. T. Lai, Y. T. Huang, C. Y. Chou, L. Y. Shih, H. W. Cheng, W. C. Wong, C. H. Ma, C., 2009, “Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(22), 8824-8829. (SCIE)
• Tsou, En-Lun, Yeh, Yao-Ting, Liang, Pi-Hui, Cheng, Wei-Chieh*, 2009, “A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP”, Tetrahedron, 65(1), 93-100. (SCIE)
• Shih, Hao-Wei, Guo, Chih-Wei, Lo, Kien-Hock, Huang, Min-Yang, Cheng, Wei-Chieh*, 2009, “Solution-Phase Parallel Synthesis of Novel Spirooxazolinoisoxazolines”, Journal of Combinatorial Chemistry, 11(2), 281-287.
• Cheng TJ, Sung MT, Liao HY, Chang YF, Chen CW, Huang CY, Chou LY, Wu YD, Chen YH, Cheng YS, Wong CH, Ma C, Cheng WC, 2008, “Domain requirement of moenomycin binding to bifunctional transglycosylases and development of high-throughput discovery of antibiotics.”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105(2), 431-6. (SCIE)
• Chang, Yi-Fan, Liu, Chen-Yu, Guo, Chih-Wei, Wang, Yen-Chih, Fang, Jim-Min, Cheng, Wei-Chieh*, 2008, “Solid-Phase Organic Synthesis of Polyisoprenoid Alcohols with Traceless Sulfone Linker”, J. Org. Chem., 73(18), 7197-7203. (SCIE)
• Tsou EL, Chen SY, Yang MH, Wang SC, Cheng TR, Cheng WC, 2008, “Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library.”, Bioorganic & medicinal chemistry, 16(24), 10198-204. (SCIE)
• Chang, Yi-Fan, Jiang, Yi-Rui, Cheng, Wei-Chieh*, 2008, “Traceless sulfone linker cleavage triggered by ozonolysis: solid-phase synthesis of diverse alpha -beta -unsaturated carbonyl compounds”, Tetrahedron Lett., 49(3), 543-547.. (SCIE)