Chemoenzymatic Preparation of 4′-Thioribose NAD+
Xiao-Nan Zhang
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorZhefu Dai
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorQinqin Cheng
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorCorresponding Author
Yong Zhang
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Research Center for Liver Diseases, University of Southern California, Los Angeles, California
Corresponding author: [email protected]Search for more papers by this authorXiao-Nan Zhang
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorZhefu Dai
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorQinqin Cheng
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Search for more papers by this authorCorresponding Author
Yong Zhang
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California
Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Research Center for Liver Diseases, University of Southern California, Los Angeles, California
Corresponding author: [email protected]Search for more papers by this authorAbstract
This chemoenzymatic procedure describes a strategy for the preparation of 4′-thioribose nicotinamide adenine dinucleotide (S-NAD+), including chemical synthesis of nicotinamide 4′-riboside (S-NR), recombinant expression and purification of two NAD+ biosynthesis enzymes nicotinamide riboside kinase (NRK) and nicotinamide mononucleotide adenylyltransferase (NMNAT), and enzymatic synthesis of S-NAD+. The first basic protocol describes the procedures for introduction of nicotinamide onto 4′-thioribose and subsequent deprotection to generate S-NR as the key intermediate for enzymatically synthesizing S-NAD+. In the second basic protocol, experimental methods are detailed for the production of recombinant human NRK1 and NMNAT1 to catalyze conversion of S-NR to S-NAD+. The third basic protocol presents the enzymatic approach for the generation of S-NAD+ from S-NR precursor. © 2019 by John Wiley & Sons, Inc.
Literature Cited
- Armstrong, J. A., & Schulz, J. R. (2015). Agarose gel electrophoresis. Current Protocols Essential Laboratory Techniques, 10, 7.2.1–7.2.22. doi: 10.1002/9780470089941.et0702s10.
10.1002/9780470089941.et0702s10 Google Scholar
- Berger, F., Lau, C., Dahlmann, M., & Ziegler, M. (2005). Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. Journal of Biological Chemistry, 280, 36334–36341. doi: 10.1074/jbc.M508660200.
- Blacher, E., Dadali, T., Bespalko, A., Haupenthal, V. J., Grimm, M. O., Hartmann, T., … Levy, A. (2015). Alzheimer's disease pathology is attenuated in a CD 38-deficient mouse model. Annals of Neurology, 78, 88–103. doi: 10.1002/ana.24425.
- Buntz, A., Wallrodt, S., Gwosch, E., Schmalz, M., Beneke, S., Ferrando-May, E., … Zumbusch, A. (2016). Real-time cellular imaging of protein poly(ADP-ribos)ylation. Angewandte Chemie International Edition, 55, 11256–11260. doi: 10.1002/anie.201605282.
- Carter-O'Connell, I., Jin, H., Morgan, R. K., David, L. L., & Cohen, M. S. (2014). Engineering the substrate specificity of ADP-ribosyltransferases for identifying direct protein targets. Journal of the American Chemical Society, 136, 5201–5204. doi: 10.1021/ja412897a.
- Carter-O'Connell, I., Jin, H., Morgan, R. K., Zaja, R., David, L. L., Ahel, I., & Cohen, M. S. (2016). Identifying family-member-specific targets of mono-ARTDs by using a chemical genetics approach. Cell Reports, 14, 621–631. doi: 10.1016/j.celrep.2015.12.045.
- Cen, Y., & Sauve, A. A. (2010). Transition state of ADP-ribosylation of acetyllysine catalyzed by Archaeoglobus fulgidus Sir2 determined by kinetic isotope effects and computational approaches. Journal of the American Chemical Society, 132, 12286–12298. doi: 10.1021/ja910342d.
- Chatterjee, S., Daenthanasanmak, A., Chakraborty, P., Wyatt, M. W., Dhar, P., Selvam, S. P., … Mehrotra, S. (2018). CD38-NAD+ axis regulates immunotherapeutic anti-tumor T cell response. Cell Metabolism, 27, 85–100. doi: 10.1016/j.cmet.2017.10.006.
- Dai, Z., Zhang, X.-N., Nasertorabi, F., Cheng, Q., Pei, H., Louie, S. G., … Zhang, Y. (2018). Facile chemoenzymatic synthesis of a novel stable mimic of NAD+. Chemical Science, 9, 8337–8342. doi: 10.1039/C8SC03899F.
- Dowden, J., Brown, R. S., Moreau, C., Galione, A., & Potter, B. V. (2005). Chemical synthesis of the novel Ca2+ messenger NAADP. Nucleosides, Nucleotides and Nucleic Acids, 24, 513–518. doi: 10.1081/NCN-200061786.
- Dowden, J., Moreau, C., Brown, R. S., Berridge, G., Galione, A., & Potter, B. V. (2004). Chemical synthesis of the second messenger nicotinic acid adenine dinucleotide phosphate by total synthesis of nicotinamide adenine dinucleotide phosphate. Angewandte Chemie International Edition, 43, 4637–4640. doi: 10.1002/anie.200460054.
- Franchetti, P., Pasqualini, M., Petrelli, R., Ricciutelli, M., Vita, P., & Cappellacci, L. (2004). Stereoselective synthesis of nicotinamide β-riboside and nucleoside analogs. Bioorganic & Medicinal Chemistry Letters, 14, 4655–4658. doi: 10.1016/j.bmcl.2004.06.093.
- Gallagher, S. R. (2012). SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Current Protocols Essential Laboratory Techniques, 6, 7.3.1–7.3.28. doi:10.1002/9780470089941.et0703s06.
10.1002/9780470089941.et0703s06 Google Scholar
- Gibson, B. A., Zhang, Y., Jiang, H., Hussey, K. M., Shrimp, J. H., Lin, H., … Kraus, W. L. (2016). Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation. Science, 353, 45–50. doi: 10.1126/science.aaf7865.
- Hassa, P. O., Haenni, S. S., Elser, M., & Hottiger, M. O. (2006). Nuclear ADP-ribosylation reactions in mammalian cells: Where are we today and where are we going? Microbiology and Molecular Biology Reviews, 70, 789–829. doi: 10.1128/MMBR.00040-05.
- Imai, S.-i., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in Cell Biology, 24, 464–471. doi: 10.1016/j.tcb.2014.04.002.
- Jeong, L. S., Lee, H. W., Jacobson, K. A., Kim, H. O., Shin, D. H., Lee, J. A., … Moon, H. R. (2006). Structure−activity relationships of 2-chloro-N6-substituted-4′-thioadenosine-5′-uronamides as highly potent and selective agonists at the human A3 adenosine receptor. Journal of Medicinal Chemistry, 49, 273–281. doi: 10.1021/jm050595e.
- Jiang, H., Congleton, J., Liu, Q., Merchant, P., Malavasi, F., Lee, H. C., … Lin, H. (2009). Mechanism-based small molecule probes for labeling CD38 on live cells. Journal of the American Chemical Society, 131, 1658–1659. doi: 10.1021/ja808387g.
- Jiang, H., Kim, J. H., Frizzell, K. M., Kraus, W. L., & Lin, H. (2010). Clickable NAD analogues for labeling substrate proteins of poly (ADP-ribose) polymerases. Journal of the American Chemical Society, 132, 9363–9372. doi: 10.1021/ja101588r.
- Khan, J. A., Xiang, S., & Tong, L. (2007). Crystal structure of human nicotinamide riboside kinase. Structure, 15, 1005–1013. doi: 10.1016/j.str.2007.06.017.
- Kuslich, C. D., Chui, B., & Yamashiro, C. T. (2018). Overview of PCR. Current Protocols Essential Laboratory Techniques, e27. doi: 10.1002/cpet.27.
- Langelier, M.-F., Zandarashvili, L., Aguiar, P. M., Black, B. E., & Pascal, J. M. (2018). NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains. Nature Communications, 9, 844. doi: 10.1038/s41467-018-03234-8.
- Lin, H. (2007). Nicotinamide adenine dinucleotide: Beyond a redox coenzyme. Organic & Biomolecular Chemistry, 5, 2541–2554. doi: 10.1039/B706887E.
- Morandi, F., Horenstein, A. L., Chillemi, A., Quarona, V., Chiesa, S., Imperatori, A., & Pistoia, V. (2015). CD56brightCD16− NK cells produce adenosine through a CD38-mediated pathway and act as regulatory cells inhibiting autologous CD4+ T cell proliferation. The Journal of Immunology, 195, 965–972. doi: 10.4049/jimmunol.1500591.
- Raffaelli, N., Sorci, L., Amici, A., Emanuelli, M., Mazzola, F., & Magni, G. (2002). Identification of a novel human nicotinamide mononucleotide adenylyltransferase. Biochemical and Biophysical Research Communications, 297, 835–840. doi: 10.1016/S0006-291X(02)02285-4.
- Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A., Mouchiroud, L., … Auwerx, J. (2016). NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Science Translational Medicine, 8, 361ra139. doi: 10.1126/scitranslmed.aaf5504.
- Ryu, K. W., Kim, D.-S., & Kraus, W. L. (2015). New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP-ribose) polymerases. Chemical Reviews, 115, 2453–2481. doi: 10.1021/cr5004248.
- Scarpa, E. S., Fabrizio, G., & Di Girolamo, M. (2013). A role of intracellular mono-ADP-ribosylation in cancer biology. The FEBS Journal, 280, 3551–3562. doi: 10.1111/febs.12290.
- Shendure, J. A., Porreca, G. J., Church, G. M., Gardner, A. F., Hendrickson, C. L., Kieleczawa, J., & Slatko, B. E. (2011). Overview of DNA sequencing strategies. Current Protocols in Molecular Biology, 96, 7.1.1–7.1.23. doi:10.1002/0471142727.mb0701s96.
10.1002/0471142727.mb0701s96 Google Scholar
- Shrimp, J. H., Hu, J., Dong, M., Wang, B. S., MacDonald, R., Jiang, H., … Lin, H. (2014). Revealing CD38 cellular localization using a cell permeable, mechanism-based fluorescent small-molecule probe. Journal of the American Chemical Society, 136, 5656–5663. doi: 10.1021/ja411046j.
- Sorci, L., Cimadamore, F., Scotti, S., Petrelli, R., Cappellacci, L., Franchetti, P., … Magni, G. (2007). Initial-rate kinetics of human NMN-adenylyltransferases: Substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis. Biochemistry, 46, 4912–4922. doi: 10.1021/bi6023379.
- Szczepankiewicz, B. G., Dai, H., Koppetsch, K. J., Qian, D., Jiang, F., Mao, C., & Perni, R. B. (2012). Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5. The Journal of Organic Chemistry, 77, 7319–7329. doi: 10.1021/jo301067e.
- Tanimori, S., Ohta, T., & Kirihata, M. (2002). An efficient chemical synthesis of nicotinamide riboside (NAR) and analogues. Bioorganic & Medicinal Chemistry Letters, 12, 1135–1137. doi: 10.1016/S0960-894X(02)00125-7.
- Tarragó, M. G., Chini, C. C. S., Kanamori, K. S., Warner, G. M., Caride, A., de Oliveira, G. C., … Chini, E. N. (2018). A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline. Cell Metabolism, 27, 1081–1095. doi: 10.1016/j.cmet.2018.03.016.
- Tempel, W., Rabeh, W. M., Bogan, K. L., Belenky, P., Wojcik, M., Seidle, H. F., … Brenner, C. (2007). Nicotinamide riboside kinase structures reveal new pathways to NAD+. PLoS Biology, 5, e263. doi: 10.1371/journal.pbio.0050263.
- Verdin, E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science, 350, 1208–1213. doi: 10.1126/science.aac4854.
- Wallrodt, S., Buntz, A., Wang, Y., Zumbusch, A., & Marx, A. (2016). Bioorthogonally functionalized NAD+ analogues for in-cell visualization of poly(ADP-ribose) formation. Angewandte Chemie International Edition, 55, 7660–7664. doi: 10.1002/anie.201600464.
- Wang, Y., Rösner, D., Grzywa, M., & Marx, A. (2014). Chain-terminating and clickable NAD+ analogues for labeling the target proteins of ADP-ribosyltransferases. Angewandte Chemie International Edition, 53, 8159–8162. doi: 10.1002/anie.201404431.
- Zatorski, A., Watanabe, K. A., Carr, S. F., Goldstein, B. M., & Pankiewicz, K. W. (1996). Chemical synthesis of benzamide adenine dinucleotide: Inhibition of inosine monophosphate dehydrogenase (types I and II). Journal of Medicinal Chemistry, 39, 2422–2426. doi: 10.1021/jm9601415.
