Faculty
Francis Johnson, Professor
Ph.D. Glasgow University, 1954
Postdoctoral Fellow, Boston University, 1954-1957
Joint appointment with Department of Pharmacological Sciences
607 Chemistry
Phone: (631) 632-8866
Email: francis.johnson@stonybrook.edu
Organic Chemistry - Medical Chemistry
The major research interests of this laboratory are concerned with a) chemical aspects of genetic toxicology and b) a program of synthesis aimed at rationally designed drugs to inhibit viral enzymes associated with HIV-1 (AIDS), c) new methods of synthesis involving organo-alkali chemistry.
Our approach to studies in genetic toxicology involves the synthesis (automated) of DNA having chemical lesions that arise physiologically from carcinogenic substances or radiation. The chief objective is to examine the mutation spectrum associated with these lesions. This is investigated both by in vitro and in vivo studies with DNA polymerases and repair enzymes. Our work so far has examined lesions associated with acrolein, carcinogenic amines, and oxidation products of both deoxyguanosine and deoxyadenosine, products that are associated with both radiation damage and asbestos-mediated transformations. In the course of this work the oxidation chemistry of the carcinogenic amine adducts has shown that at physiological pH a slow oxygen-induced degradation takes place, producing an array of intermediates derived from the initial adduct. The role of these secondary lesions in carcinogenesis is under investigation. In addition, new protecting groups for the synthesis of DNA containing these lesions have had to be designed to accommodate the extreme sensitivity of a number of these adducts to the normal chemistry of DNA synthesis.
In the area of AIDS research, we have been successful in designing new substances that interfere with the reverse transcriptase responsible for the viral DNA/RNA replication. These substances constitute a new class of anti-viral agents in that they inhibit the viral reverse transcriptase at the active site and appear to be irreversible in action. They are active against a range of other viruses, but do not inhibit the cellular DNA synthetases of mammalian cells.
The third area of research concerns new synthetic methods. Here, we have discovered a new type of directed ortho-metalation cyclization that allows the easy synthesis of a wide variety of indenediones. Previously, synthetic methods for the preparation of this class of compound were limited to the simplest members of the group. Some of the new compounds are now being tested for anticoagulant and antibiotic activity.
Publications
Chemically-modified curcumin 2.24: a novel systemic therapy for natural periodontitis in dogs. Deng J; Golub LM Lee H-M; Lin MC; Bhatt HD; Hong H-L; Johnson F; Scaduto J; Zimmerman T; Gu Y. Journal of Experimental Pharmacology (2020), 12, 47-60, PMID: 32104105
Enhanced efficacy of chemically modified curcumin in experimental periodontitis: systemic implications. Wang HH; Lee H-M; Raja V; Hou W; Iacono VJ; Scaduto J; Johnson F; Golub LM; Gu Y. Journal of Experimental Pharmacology (2019), 11, 1-14, PMID: 30774454
Targeted and Untargeted Detection of DNA Adducts of Aromatic Amine Carcinogens in Human Bladder by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry. Guo J; Villalta PW; Weight CJ; Bonala R; Johnson F; Rosenquist TA; Turesky RJ. Chemical Research in Toxicology (2018), 31(12), 1382-1397, PMID: 30387604
A Chemically Modified Curcumin (CMC 2.24) Inhibits Nuclear Factor κB Activation and Inflammatory Bone Loss in Murine Models of LPS-Induced Experimental Periodontitis and Diabetes-Associated Natural Periodontitis. Elburki MS; Rossa C Jr; Guimaraes-Stabili MR; Lee H-M; Curylofo-Zotti FA; Johnson F; Golub LM. Inflammation (2017), 40(4), 1436-144, PMID: 28534138
Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial. Chung V; Mansfield AS; Braiteh F; Richards D; Durivage H; Ungerleider RS.; Johnson F; Kovach JS. Cancer Research (2017), 23(13), 3277-3284, PMID: 28039265
A novel chemically modified curcumin "normalizes" wound-healing in rats with experimentally induced type I diabetes: initial studies. Zhang Y; McClain SA; Lee H-M; Elburki MS; Yu H; Gu Y; Zhang Y; Wolff M; Johnson F; Golub LM. Journal of Diabetes Research (2016), 5782904/1-5782904/11, PMID: 27190999
Total Synthesis of the Aristolochic Acids, Their Major Metabolites, and Related Compounds. Attaluri S; Iden CR; Bonala Radha R; Johnson F. Chemical Research in Toxicology (2014), 27(7), 1236-1242, PMID: 24877584
Prostate cancer stem cell-targeted efficacy of a new-generation taxoid, SBT-1214 and novel polyenolic zinc-binding curcuminoid, CMC2.24. Botchkina GI; Zuniga ES; Rowehl RH; Park R; Bhalla R; Bialkowska AB; Johnson F; Golub LM; Zhang Y; Ojima I; et al. PloS one (2013), 8(9), e69884, PMID: 24086245
Design, synthesis and biological activity of new polyenolic inhibitors of matrix metalloproteinases: a focus on chemically-modified curcumins. Zhang Y; Gu Y; Lee H-M; Hambardjieva E; Vrankova Ka; Golub, Lorne M.; Johnson, Francis. Current Medicinal Chemistry (2012), 19(25), 4348-4358, PMID: 22830350
The Antibiotic Thermorubin Inhibits Protein Synthesis by Binding to Inter-Subunit Bridge B2a of the Ribosome. Bulkley D; Johnson F; Steitz TA. Journal of Molecular Biology (2012), 416(4), 571-578, PMID: 22240456
Novel post-synthetic generation, isomeric resolution, and characterization of Fapy-dG within oligodeoxynucleotides: differential anomeric impacts on DNA duplex properties. Lukin M; Minetti CASA; Remeta DP; Attaluri S; Johnson F; Breslauer KJ; de los Santos C. Nucleic Acids Research (2011), 39(13), 5776-5789, PMID: 21415012
Structure-activity relationship study of novel anticancer aspirin-based compounds. Joseph S; Nie T; Huang L; Zhou H; Atmakur K; Gupta RC; Johnson F; Rigas, B. Molecular Medicine Reports (2011), 4(5), 891-899, PMID: 21805049
Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms. Lu J; Kovach JS; Johnson F; Chiang J; Hodes R; Lonser R; Zhuang Z. Proceedings of the National Academy of Sciences, USA (2009), 106(28), 11697-11702, PMID: 19564615
3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. Gelmi ML; Pocar D; Pontremoli G; Pellegrino S; Bombardelli E; Fontana G; Riva A; Balduini W; Carloni S; Cimino M; et al. Journal of medicinal chemistry (2006), 49(18), 5571-7, PMID: 16942030
Inhibition of the Bacterial Enoyl Reductase FabI by Triclosan: A Structure-Reactivity Analysis of FabI Inhibition by Triclosan Analogues. Sivaraman S; Sullivan, TJ; Johnson F; Novichenok P; Cui G; Simmerling C; Tonge PJ. Journal of Medicinal Chemistry (2004), 47(3), 509-518, PMID: 14736233
Application of vicarious nucleophilic substitution to the total synthesis of dl-physostigmine. Rege PD; Johnson F. The Journal of organic chemistry (2003), 68(16), 6133-9, PMID: 12895041
Efficient synthesis of the benzo[a]pyrene metabolic adducts of 2'-deoxyguanosine and 2'-deoxyadenosine and their direct incorporation into DNA. Johnson F; Bonala R; Tawde D; Torres MC; Iden CR. Chemical research in toxicology (2002), 15(12), 1489-94, PMID: 12482230
A New Method for the Postsynthetic Generation of Abasic Sites in Oligomeric DNA. Shishkina IG; Johnson, F. Chemical Research in Toxicology (2000), 13(9), 907-912, PMID: 10995264