eBriefing

Click Chemistry in Biology and Medicine

Click Chemistry in Biology and Medicine
Reported by
Megan Stephan

Posted November 21, 2014

Overview

Click chemistry is a new approach to synthetic organic chemistry that uses simple chemical building blocks and mild aqueous conditions to produce high-specificity ligands and labeling molecules for the investigation of biological systems. These reactions mimic those found in nature for building large complex molecules such as proteins, DNA, and RNA. Since its inception by K. Barry Sharpless, click chemistry has yielded several novel reactions that have been used to produce experimental tools and therapeutic agents, some of which are now in preclinical testing. The products of these reactions are particularly useful for investigating difficult-to-synthesize biological products such as glycans, and challenging, highly transient signaling activities such as those depending on redox reactions. On September 15, 2014, pioneers and young investigators in the field presented their recent work, providing a glimpse into the expanding possibilities of this synthetic methodology. The symposium, Click Chemistry in Biology and Medicine: New Developments and Strategies, was presented by the Academy's Chemical Biology Discussion Group.

Use the tabs above to find a meeting report and multimedia from this event.

Presentation available from:
Jim Paulson, PhD (Scripps Research Institute)


The Chemical Biology Discussion Group is proudly supported by   American Chemical Society


Mission Partner support for the Frontiers of Science program provided by   Pfizer

Journal Articles

Yimon Aye

Fang X, Fu Y, Long MJ, et al. Temporally controlled targeting of 4-hydroxynonenal to specific proteins in living cells. J Am Chem Soc. 2013;135:14496-9.

Jim Paulson

Kawasaki N, Rillahan CD, Cheng TY, et al. Targeted delivery of mycobacterial antigens to human dendritic cells via Siglec-7 induces robust T cell activation. J Immunol. 2014;193:1560-6.

Macauley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014;14:653-66.

Pfrengle F, Macauley MS, Kawasaki N, et al. Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22. J Immunol. 2013;191:1724-31.

Rillahan CD, Macauley MS, Schwartz E, et al. Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukaemias and B cell lymphomas. Chem Sci. 2014;5:2398-406.

Rillahan CD, Schwartz E, McBride R, et al. Click and pick: identification of sialoside analogues for siglec-based cell targeting. Angew Chem Int Ed Engl. 2012;51:11014-8.

Rillahan CD, Schwartz E, Rademacher C, et al. On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7. ACS Chem Biol. 2013;8:1417-22.

K. Barry Sharpless

Dong J, Krasnova L, Finn MG, et al. Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry. Angew Chem Int Ed Engl. 2014;53:9430-48.

Dong J, Sharpless KB, Kwisnek L, et al. SuFEx-based synthesis of polysulfates. Angew Chem Int Ed Engl. 2014;53:9466-70.

Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl. 2001;40(11):2004-21.

Kolb HC, Sharpless KB. The growing impact of click chemistry on drug discovery. Drug Discov Today. 2003;8(24):1128-37. Review.

Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew Chem Int Ed Engl. 2002;41(14):2596-9.

Sharpless KB, Manetsch R. In situ click chemistry: a powerful means for lead discovery. Expert Opin Drug Discov. 2006;1(6):525-38.

David A. Spiegel

Jakobsche CE, Parker CG, Tao RN, et al. Exploring binding and effector functions of natural human antibodies using synthetic immunomodulators. ACS Chem Biol. 2013;8:2404-11.

McEnaney PJ, Parker CG, Zhang AX, et al. Antibody-recruiting molecules: an emerging paradigm for engaging immune function in treating human disease. ACS Chem Biol. 2012;7:1139-51.

Murelli RP, Zhang AX, Michel J, et al. Chemical control over immune recognition: a class of antibody-recruiting small molecules that target prostate cancer. J Am Chem Soc. 2009;131:17090-2.

Spiegel DA. A call to ARMs: the promise of immunomodulatory small molecules. Expert Rev Clin Pharmacol. 2013;223-5.

Wang T, Kartika R, Spiegel DA. Exploring post-translational arginine modification using chemically synthesized methylglyoxal hydroimidazolones. J Am Chem Soc. 2012;134:8958-67.

Peng Wu

Jiang H, Feng L, Soriano del Amo D, et al. Imaging glycans in zebrafish embryos by metabolic labeling and bioorthogonal click chemistry. J Vis Exp. 2011;(52).

Jiang H, Zheng T, Lopez-Aguilar A, et al. Monitoring dynamic glycosylation in vivo using supersensitive click chemistry. Bioconjug Chem. 2014;25:698-706.

Li B, Mock F, Wu P. Imaging the glycome in living systems. Methods Enzymol. 2012;505:401-19.

Rouhanifard SH, Nordstrom LU, Zheng T, et al. Chemical probing of glycans in cells and organisms. Chem Soc Rev. 2013;42:4284-96.

Zheng T, Jiang H, Gros M, et al. Tracking N-acetyllactosamine on cell-surface glycans in vivo. Angew Chem Int Ed Engl. 2011;50:4113-8.


Reviews and Reports

Glen Research: Products for DNA Research. More click chemistry. Glen Reports. 2014.

King A. Unnatural DNA links click for faster synthesis. ChemistryWorld. Royal Society of Chemistry. 2014.

Li H, Aneja R, Chaiken I. Click chemistry in peptide-based drug design. Molecules. 2013;18(8):9797-817. Review.

Life Technologies. Chapter 3: Click Chemistry and Other Functional Group Modifications. In: Johnson I, Spence MTZ, eds. Molecular Probes Handbook—A Guide to Fluorescent Probes and Labeling Technologies. 11th ed. 2010.

Mah R, Thomas JR, Shafer CM. Drug discovery considerations in the development of covalent inhibitors. Bioorg Med Chem Lett. 2014;24(1):33-9. Review.

Thundimadathil J. New reactions with click chemistry. R&D Magazine. 2012.

Zeng D, Zeglis BM, Lewis JS, Anderson CJ. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals. J Nucl Med. 2013;54(6):829-32. Review.

Organizers

Peng Wu, PhD

Albert Einstein College of Medicine
website | publications

Peng Wu is an associate professor in the Department of Biochemistry and the director of the newly established Chemical Biology Core Facility at the Albert Einstein College of Medicine. He received his PhD from Scripps Research Institute in 2005 under the guidance of K. Barry Sharpless. He also spent time as a visiting student in the laboratory of Professor Craig J. Hawker at IBM Almaden Research Center and at the University of California, Santa Barbara. Wu was a postdoctoral fellow in the group of Dr. Carolyn R. Bertozzi at the University of California, Berkeley. Since joining the Albert Einstein College of Medicine in 2008, Wu has focused on developing a research program at the interface of chemistry and biology, particularly the invention of new tools for studying protein glycosylation related to human disease.

Jennifer Henry, PhD

The New York Academy of Sciences

Jennifer Henry is the former director of Life Sciences at the New York Academy of Sciences. Before joining the Academy, she was a publishing manager in the Academic Journals division at Nature Publishing Group. She also served for eight years as editor of Functional Plant Biology for CSIRO Publishing in Australia. She received her PhD in plant molecular biology from the University of Melbourne, specializing in the genetic engineering of transgenic crops. As director of Life Sciences, she developed scientific symposia across a range of life sciences, including biochemical pharmacology, neuroscience, systems biology, genome integrity, infectious diseases and microbiology. She also generated alliances with organizations interested in developing programmatic content.


Keynote Speakers

Jim Paulson, PhD

Scripps Research Institute
website | publications

James C. Paulson obtained his PhD in biochemistry from the University of Illinois at Champaign–Urbana and did postdoctoral work at Duke University Medical Center. From 1978 to 1990 he was a member of the faculty in the Department of Biological Chemistry at the UCLA School of Medicine, where he developed an interest in analyzing the receptor specificity of influenza viruses from different host species. From 1990 to 1999 he served as vice president and a member of the Board of Directors at Cytel Corporation. Since 1999 he has been a professor at Scripps Research Institute, where he is chair of the Department of Cell and Molecular Biology with joint appointments in the Department of Chemical Physiology and the Department of Immunology and Microbial Sciences. His current research interests include the roles of glycan binding proteins in the modulation of immune cell signaling and the receptor specificity of mammalian and animal influenza viruses.

K. Barry Sharpless, PhD

Scripps Research Institute
website | publications

K. Barry Sharpless holds a PhD in organic chemistry from Stanford University and completed postdoctoral studies with Dr. J. P. Collman, also at Stanford, and with Dr. Konrad Bloch at Harvard University. Sharpless set up his own laboratory in 1970 at Massachusetts Institute of Technology. Except for several years in the 1970s when he was a member of Stanford's chemistry faculty, Sharpless remained at MIT until moving to Scripps Research Institute in 1990. At Scripps he is W. M. Keck Professor of Chemistry and a member of the Skaggs Institute for Chemical Biology. In 2011 Thomson Reuters named him fourth on the list of top 100 chemists whose papers published in the first decade of the 21st century achieved the highest citation impact scores. In 2001 Sharpless shared the Nobel Prize in Chemistry for his work on chirally catalyzed oxidation reactions (Sharpless epoxidation, Sharpless asymmetric dihydroxylation, Sharpless oxyamination). The other half of the prize was shared by Drs. William S. Knowles and Ryōji Noyori for their work on stereoselective hydrogenation.


Speakers

Yimon Aye, PhD

Cornell University
website | publications

Yimon Aye received her PhD in organic chemistry from Harvard University in 2009 under the guidance of Dr. David Evans. As a Damon Runyon cancer research postdoctoral fellow, she received training in mechanistic biology at Massachusetts Institute of Technology, mentored by Dr. JoAnne Stubbe. She is now the Milstein Junior Faculty Fellow and an assistant professor in the Department of Chemistry and Chemical Biology at Cornell University with a secondary appointment in the Department of Biochemistry at Weill Cornell Medical College. Aye established her laboratory at Cornell University in July 2012 and was recently recognized by the National Science Foundation CAREER and Beckman Young Investigator Awards.

David A. Spiegel, MD, PhD

Yale University
website | publications

David A. Spiegel is an associate professor at Yale University with appointments in the Departments of Chemistry and Pharmacology. He pursued a combined MD/PhD degree at Yale University, where he focused on synthetic organic chemistry, graduating in 2005. After postdoctoral studies at the Broad Institute of Harvard and MIT, Spiegel started his independent academic career at Yale University in 2007. His research group works on synthetic immunology, which involves the development of novel synthetic systems for modulating and manipulating immune function. Specific disease areas of interest include prostate cancer, HIV, Gram-positive bacteria, and aging. Spiegel has received awards including the NIH Director's New Innovator Award, the Department of Defense Era of Hope Scholar Award, the Ellison Medical Foundation New Scholar Award in Aging Research, the Novartis Early Career Award in Organic Chemistry, the Bill and Melinda Gates Foundation Grand Challenges Explorations Award, and the Alfred P. Sloan Foundation Fellowship.

Mingxuan Wu, MS

Princeton University
website | publications

Mingxuan Wu received his BS in biotechnology and MS in microbiology from Shanghai Jiao Tong University, China. Under the direction of Professor Huchen Zhou in the School of Pharmacy, he synthesized sugar nucleotides to study antibiotic glycosylation and diterpenoid probes to elucidate the mechanism of leukemia cell differentiation. In 2010, he joined the Fiedler lab in the Department of Chemistry at Princeton University to study diphosphoinositol polyphosphate signaling by non-hydrolyzable analogs and affinity reagents.

Peng Wu, PhD

Albert Einstein College of Medicine
website | publications

Megan Stephan

Megan Stephan studied transporters and ion channels at Yale University for nearly two decades before giving up the pipettor for the pen. She specializes in covering research at the interface between biology, chemistry, and physics. Her work has appeared in The Scientist and Yale Medicine. Stephan holds a PhD in biology from Boston University.

Sponsors

Academy Friends

Avanti Polar Lipids

New England Biolabs


The Chemical Biology Discussion Group is proudly supported by   American Chemical Society


Mission Partner support for the Frontiers of Science program provided by   Pfizer