个人简介

Graham B. Jones is Professor and Chair of Chemistry & Chemical Biology and Co-Director of the Barnett Institute of Chemical & Biological Analysis at Northeastern University in Boston, Massachusetts, USA. Jones was educated in the UK, receiving BSc and PhD degrees in chemistry from the University of Liverpool and the Imperial College of Science Technology and Medicine respectively. He then moved to the USA as a NATO fellow and conducted independent research at Harvard University with E. J. Corey, the 1990 Nobelist in chemistry. His research expertise lies at the interface of organic and medicinal chemistry, and has resulted in over 120 publications, generated in excess of $30M external funding and forged numerous collaborative partnerships with the pharmaceutical and biotechnology industry. He has been appointed to several editorial posts for scholarly scientific journals, and was awarded the DSc degree in 2006 for his contributions to medicinal chemistry. Graham has held a variety of influential executive positions in the academic sector both in the UK and USA. These include Directorship of the Northeastern Biotechnology Initiative, as the Pro-Vice Chancellor for Enterprise at the University of Hull.

研究领域

Bioorganic and Medicinal Chemistry

Professor Jones’ research group is dedicated to the application of synthetic organic chemistry to the development of diagnostic and therapeutic agents. Since the mid-90’s the program has produced over 120 original research publications and attracted over $8 million in research funding. In most cases projects represent joint efforts between our NU program (housed in the Bioorganic & Medicinal Chemistry Laboratory) and collaborators at the nearby Harvard Medical School. Current projects include: Targeted delivery and activation of cytotoxic antitumor agents. The Jones group pioneered a new method for the synthesis of enediyne prodrugs and continues to develop targeted variants. The first FDA approved monoclonal antibody-cytotoxin conjugate (MylotargÒ) was an enediyne derivative and interest in this fascinating class of agents continues to inspire the oncology research community. The cycloaromatization of enediynes results in generation of cytotoxic diradicals, which induce DNA strand scission and can also induce proteolysis. Expanding the versatility of the enediyne family, we recently developed methodology for coupling of photo-activated enediynes to both monoclonal antibodies and gold nanoparticles via PEG linker chemistry. The bioconjugated agents retain their photoactivation profiles and immunocompetence and are under investigation for potential as topically applied antiproliferative agents. Drug targeting of bulged DNA and RNA microenvironments. A variety of neurodegenerative diseases (Huntington’s disease, Freiderich ataxia, fragile X syndrome) are believed to be related to defects in DNA which result in slipped synthesis. It has been suggested that the slippage process is linked to bulged defects in the DNA, and it has become of interest to design and synthesize molecules, which have the ability to recognize these bulges with high affinity. Using the natural product metabolite NCSi-gb as a lead compound a series of spirocyclic agents were designed, synthesized and then optimized for binding to specific 2 base bulged targets. The current lead compound (derived from a 23 step synthesis) binds to a TG bulged with 80 nM affinity, the most effective synthetic agent yet reported. Related to this program, replication of HIV-1 involves binding of the tat protein to an RNA sequence and subsequent formation of an antitermination complex. The tat binding site constitutes a 3 base bulge, and preliminary data confirms that our synthetic compounds have sub-micromolar affinity for these key targets. Rapid labeling methodology for SPECT and PET imaging. Molecular imaging methods are playing an increasingly significant role in drug development, creating a need for versatile and efficient methodology to introduce appropriate radiolabels. In collaboration with the Center for Translational Imaging at Northeastern, and backed by corporate partners, the Jones Group is developing methodology for rapid labeling of drugs for PET and SPECT imaging using F18 and I125 nuclides respectively. For example, methodology has been developed for microwave-accelerated halodenitrations as well as tandem Hiyama coupling halo-alkylations. This methodology has been extended recently to include nitro-dehalogenation allowing us to develop complimentary radiolabeling strategies. Efficient catalytic methods for synthesis of medicinal agents. Our group has a long-standing tradition of developing original synthetic methods, reagents, and catalysts to solve problems of significance in drug development. Very recently, a method for production of xanthine derivatives related to KW-6002 (istradefylline) was developed. This compound is under clinical investigation for the treatment of Parkinson’s disease in combination with levodopa. The new method allows one pot synthesis of the xanthine core and eliminates the need for external oxidants. The method provides facile and direct access to numerous analogues of this class, which are currently the subject of a pre-clinical investigation.

近期论文

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History of Anticancer Drugs. Jones, G.B. eLS. 2014, John Wiley & Sons Ltd. DOI: 10.1002/9780470015902.a0003630.pub2. Flow and Microwave Assisted Synthesis of Medicinally Relevant Indoles. Ranasinghe, N., and Jones, G.B. Current Green Chemistry. 2014, Early Online. Novel Approaches for Targeting the Adenosine A2A Receptor. Yuan, G., Gedeon, N.G., Jankins, T.C., and Jones, G.B. Expert Opinion in Drug Discovery. 2014, Early Online. A Facile Route to Triazolopyrimidines Using a [3+2] Cycloaddition and Continuous Flow Chemistry.Sadler, S., Sebeika, M.M., Kern, N.L., Bell, D.E., Laverack, C.A., Wilkins, D.J., Moeller, A.R., Nicolaysen, B.C., Kozlowski, P.N., Wiles, C., Tinder, R.J. and Jones, G.B. Journal of Flow Chemistry. 2014, 4(3), 140-147. Towards Next Generation Adenosine A2A Receptor Antagonists. Yuan, G. and Jones, G.B. Current Medicinal Chemistry 2014, 21(34), 3918-3935. Safer, Greener, and more Facile Alternatives for Synthesis of Organic Azides. Sebeika, M.M.; Jones, G.B. Current Organic Synthesis. 2014. 11(5), 732-750. Accelerated Labeling Methods and Syntheses of Radiotracers Utilizing Microfluidic Technology. Hargrove, K.; Jones, G.B. Current Radiopharmaceuticals. 2014. 7(1), 36-48. Hypoxia-induced and A2A adenosine receptor-independent T-cell suppression is short lived and easily reversible. Ohta, A.; Madasu, M.; Subramanian, M.; Kini, R.; Jones, G.; Chouker, A.; Ohta, A.; Sitkovsky, M. International Immunology. 2014, 26, 83-91. Design and evaluation of xanthine based adenosine receptor antagonists: Potential hypoxia targeted immunotherapies. Thomas, R.; Lee, J.; Chevalier, V.; Sadler, S.; Selesniemi, K.; Hatfield, S.; Sitkovsky, M.; Ondrechen, M. J.; Jones, G. B. Bioorganic & Medicinal Chemistry. 2013, 21, 7453-7464. Fluoroalkynylations of Aryl Halides under Continuous-Flow Homogeneous Catalysts. Placzek, M.S.; Chmielecki, J.M.; Houghton, C.; Calder, A.; Wiles, C.; Jones, G.B. J. Flow Chem. 2013, 3(2), 46-50. Extending the versatility of the Hemetsberger-Knittel indole synthesis through microwave and flow chemistry. Ranasinghe, N.; Jones, G. B., Bioorg. Med. Chem. Lett. 2013, 23(6), 1740-1742. Microwave and continuous flow technologies in drug discovery. Sadler, S.; Moeller, A.R.; Jones, G.B. Expert Opinion in Drug Discovery. 2012, 7(12), 1107-1128. The Forward Path for Biopharmaceuticals and Biosimilars: Emerging Options in the Selection of Host Cell Systems. Wager, K.; Jones, G.B. Current Biotechnology. 2012, 1(4), 297-317. Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars. Berkowitz, Steven A.; Engen, John R.; Mazzeo, Jeffrey R.; Jones, Graham B. Nature Reviews Drug Discovery, 2012, 11, 527-540. Synthesis and evaluation of potent and selective human V1a receptor antragonists as potential ligands for PET or SPECT imaging. Fabio, Karine; Guillon, Christophe; Lacey, Carl J.; Lu, Shi-fang; Heindel, Ned D.; Ferris, Craig F.; Placzek, Michael; Jones, Graham; Brownstein, Michael J.; Simon, Neal G. Bioorganic and Medicinal Chemistry, 2012, 20, 1337-1345. Microwave Accelerated Labeling Methods in the Synthesis of Radioligands for Positron Emission Tomography Imaging, Kallmerten, Amy; Alexander, Abigail; Wager, Krista; Jones, Graham, Current Radiopharmaceuticals, 2011, 4 (4), 343-354 Internalization of C17α-alkynylestradiol-porphyrin conjugates into estrogen receptor positive MCF-7 breast cancer cells, Sadler, Sara; Persons, Kelly S.; Jones, Graham B.; Ray, Rahul, Bioorganic and Medicinal Chemistry Letters, 2011, 21(15), 4638-4641. Microwave accelerated three-component fluoroalkylations: expeditious routes to fluoropharmaceuticals and PET ligands, Placzek, Michael; LaBeaume, Paul; Harris, Luke; Ng, Patrick; Daniels, Mathew; Kallmerten, Amy; Jones, Graham B., Tetrahedron Letters, 2011, 52, 332. An efficient route to xanthine based A2A adenosine receptor antagonists and functional derivatives, LaBeaume, Paul; Dong, Ma; Sitkovsky, Michail; Jones, Elizabeth V.; Thomas, Rhiannon; Sadler, Sara; Kallmerten, Amy E.; Jones, Graham B. Organic and Biomolecular Chemistry, 2010, 8, 4155. Radio-Iodination Methods for the Production of SPECT Imaging Agents, Wager, K., Jones, G.B., Current Radiopharmaceuticals, 2010, 3 (1) 37.