U.S. Department of Health and Human Services

Laboratory of Bioorganic Chemistry

Kenneth A. Jacobson, Ph.D., Chief


A selection of recent and significant publications can be viewed below.

Nakajima K, Cui Z, Li C, Meister J, Cui Y, Fu O, Smith AS, Jain S, Lowell BB, Krashes MJ, Wess J. Corrigendum: Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat Commun. 2016 Mar 3; 7 (7; 2016 Mar 3):11019. [Full Text/Abstract]
Janowsky A, Tosh DK, Eshleman AJ, Jacobson KA. Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine. J Pharmacol Exp Ther. 2016 Jan 26; 357 (2016 Jan 26; 357; 1):24-35. [Full Text/Abstract]
Rossi M, Ruiz de Azua I, Barella LF, Sakamoto W, Zhu L, Cui Y, Lu H, Rebholz H, Matschinsky FM, Doliba NM, Butcher AJ, Tobin AB, Wess J. CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo. Proc Natl Acad Sci U S A. 2015 Nov 23; 112 (49; 2015 Nov 23; 112):E6818-24. [Full Text/Abstract]
Jacobson KA. New paradigms in GPCR drug discovery. Biochem Pharmacol. 2015 Aug 8; 98 (98; 4; 2015 Aug 8):541-555. [Full Text/Abstract]
Sayeed MA, Bufano MK, Xu P, Eckhoff G, Charles RC, Alam MM, Sultana T, Rashu MR, Berger A, Gonzalez-Escobedo G, Mandlik A, Bhuiyan TR, Leung DT, LaRocque RC, Harris JB, Calderwood SB, Qadri F, Vann WF, Kováč P, Ryan ET. A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice. PLoS Negl Trop Dis. 2015 Jul; 9 (2015 Jul; 7; 9):e0003881. [Full Text/Abstract]
Soliman SE, Kováč P. Stereoselective Syntheses of the Conjugation-Ready, Downstream Disaccharide and Phosphorylated Upstream, Branched Trisaccharide Fragments of the O-PS of Vibrio cholerae O139. J Org Chem. 2015 Apr 30; 80 (80; 10; 2015 Apr 30):4851-60. [Full Text/Abstract]
Ford A, Castonguay A, Cottet M, Little JW, Chen Z, Symons-Liguori AM, Doyle T, Egan TM, Vanderah TW, De Konnick Y, Tosh DK, Jacobson KA, Salvemini D. Engagement of the GABA to KCC2 signaling pathway contributes to the analgesic effects of A3AR agonists in neuropathic pain. J Neurosci. 2015 Apr 15; 35 (35; 15; 2015 Apr 15):6057-67. [Full Text/Abstract]
Jacobson KA, Paoletta S, Katritch V, Wu B, Gao ZG, Zhao Q, Stevens RC, Kiselev E. Nucleotides Acting at P2Y Receptors: Connecting Structure and Function. Mol Pharmacol. 2015 Apr 2; 88 (2; 2015 Apr 2; 88):220-30. [Full Text/Abstract]
Zhang D, Gao ZG, Zhang K, Kiselev E, Crane S, Wang J, Paoletta S, Yi C, Ma L, Zhang W, Han GW, Liu H, Cherezov V, Katritch V, Jiang H, Stevens RC, Jacobson KA, Zhao Q, Wu B. Two disparate ligand-binding sites in the human P2Y1 receptor. Nature. 2015 Mar 30; 520 (520; 2015 Mar 30; 7547):317-21. [Full Text/Abstract]
Ivers LC, Charles RC, Hilaire IJ, Mayo-Smith LM, Teng JE, Jerome JG, Rychert J, LaRocque RC, Xu P, Kovácˇ P, Ryan ET, Qadri F, Almazor CP, Franke MF, Harris JB. Immunogenicity of the Bivalent Oral Cholera Vaccine Shanchol in Haitian Adults With HIV Infection. J Infect Dis. 2015 Feb 26; 212 (212; 2015 Feb 26; 5):779-83. [Full Text/Abstract]
Xu P, Stevens ED, French AD, Kováč P. Synthesis and molecular structure of the 5-methoxycarbonylpentyl α-glycoside of the upstream, terminal moiety of the O-specific polysaccharide of Vibrio cholerae O1, serotype Inaba. Molecules. 2015 Feb 11; 20 (20; 2; 2015 Feb 11):2892-902. [Full Text/Abstract]
Tosh DK, Finley A, Paoletta S, Moss SM, Gao ZG, Gizewski ET, Auchampach JA, Salvemini D, Jacobson KA. In vivo phenotypic screening for treating chronic neuropathic pain: modification of c2-arylethynyl group of conformationally constrained a3 adenosine receptor agonists. J Med Chem. 2014 Nov 25; 57 (2014 Nov 25; 23; 57):9901-14. [Full Text/Abstract]
Jacobson KA, Costanzi S, Paoletta S. Computational studies to predict or explain G protein coupled receptor polypharmacology. Trends Pharmacol Sci. 2014 Nov 14; 35 (35; 2014 Nov 14; 12):658-63. [Full Text/Abstract]
Zhao C, Hoppe T, Setty MK, Murray D, Chun TW, Hewlett I, Appella DH. Quantification of plasma HIV RNA using chemically engineered peptide nucleic acids. Nat Commun. 2014 Oct 6; 5 (2014 Oct 6; 5):5079. [Full Text/Abstract]
Ciruela F, Jacobson KA, Fernández-Dueñas V. Portraying g protein-coupled receptors with fluorescent ligands. ACS Chem Biol. 2014 Jul 28; 9 (2014 Jul 28; 9):1918-28. [Full Text/Abstract]
Englund EA, Gupta P, Micklitsch CM, Onyshchenko MI, Remeeva E, Neumann RD, Panyutin IG, Appella DH. PPG peptide nucleic acids that promote DNA guanine quadruplexes. Chembiochem. 2014 Jul 8; 15 (15; 13; 2014 Jul 8):1887-90. [Full Text/Abstract]
Dix AV, Moss SM, Phan K, Hoppe T, Paoletta S, Kozma E, Gao ZG, Durell SR, Jacobson KA, Appella DH. Programmable Nanoscaffolds That Control Ligand Display to a G-Protein-Coupled Receptor in Membranes To Allow Dissection of Multivalent Effects. J Am Chem Soc. 2014 Aug 25; 136 (35; 2014 Aug 25; 136):12296-303. [Full Text/Abstract]
Leung CT, Li A, Banerjee J, Gao ZG, Kambayashi T, Jacobson KA, Civan MM. The role of activated adenosine receptors in degranulation of human LAD2 mast cells. Purinergic Signal. 2014 Mar 5; 10 (2014 Mar 5; 10; 3):465-75. [Full Text/Abstract]
Vassilopoulos A, Xiao C, Chisholm C, Chen W, Xu X, Lahusen TJ, Bewley C, Deng CX. Synergistic Therapeutic Effect of Cisplatin and Phosphatidylinositol 3-Kinase (PI3K) Inhibitors in Cancer Growth and Metastasis of Brca1 Mutant Tumors. J Biol Chem. 2014 Jul 8; 289 (35; 289; 2014 Jul 8):24202-14. [Full Text/Abstract]
Gao ZG, Balasubramanian R, Kiselev E, Wei Q, Jacobson KA. Probing Biased/Partial Agonism at the G Protein-Coupled A2B Adenosine Receptoř. Biochem Pharmacol. 2014 Aug 1; 90 (2014 Aug 1; 3; 90):297-306. [Full Text/Abstract]
Toti KS, Moss SM, Paoletta S, Gao ZG, Jacobson KA, Van Calenbergh S. Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators. Bioorg Med Chem. 2014 Aug 1; 22 (15; 2014 Aug 1; 22):4257-68. [Full Text/Abstract]
Tosh DK, Paoletta S, Chen Z, Moss SM, Gao ZG, Salvemini D, Jacobson KA. Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor. Bioorg Med Chem Lett. 2014 Aug 1; 24 (15; 2014 Aug 1; 24):3302-6. [Full Text/Abstract]
Ochoa-Cortes F, Liñán-Rico A, Jacobson KA, Christofi FL. Potential for Developing Purinergic Drugs for Gastrointestinal Diseases. Inflamm Bowel Dis. 2014 Jul; 20 (20; 7; 2014 Jul):1259-87. [Full Text/Abstract]
Kruse AC, Kobilka BK, Gautam D, Sexton PM, Christopoulos A, Wess J. Muscarinic acetylcholine receptors: novel opportunities for drug development. Nat Rev Drug Discov. 2014 Jul; 13 (7; 13; 2014 Jul):549-60. [Full Text/Abstract]
Kruse AC, Hu J, Kobilka BK, Wess J. Muscarinic acetylcholine receptor X-ray structures: potential implications for drug development. Curr Opin Pharmacol. 2014 Jun; 16 (16; 2014 Jun):24-30. [Full Text/Abstract]
Jayasekara PS, Barrett MO, Ball CB, Brown KA, Hammes E, Balasubramanian R, Harden TK, Jacobson KA. 4-Alkyloxyimino Derivatives of Uridine-5'-triphosphate: Distal Modification of Potent Agonists as a Strategy for Molecular Probes of P2Y2, P2Y4, and P2Y6 Receptors. J Med Chem. 2014 May 8; 57 (9; 2014 May 8; 57):3874-83. [Full Text/Abstract]
Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, Moss SM, Paoletta S, Kiselev E, Lu W, Fenalti G, Zhang W, Müller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q. Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature. 2014 May 1; 509 (2014 May 1; 509; 7498):115-8. [Full Text/Abstract]
Yang T, Shen JB, Yang R, Redden J, Dodge-Kafka K, Grady J, Jacobson KA, Liang BT. A Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure. Circ Heart Fail. 2014 May; 7 (7; 2014 May; 3):510-8. [Full Text/Abstract]
Uddin T, Aktar A, Xu P, Johnson RA, Rahman MA, Leung DT, Afrin S, Akter A, Alam MM, Rahman A, Chowdhury F, Khan AI, Bhuiyan TR, Bufano MK, Rashu R, Yu Y, Wu-Freeman Y, Harris JB, Larocque RC, Charles RC, Kovač P, Calderwood SB, Ryan ET, Qadri F. Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera. Am J Trop Med Hyg. 2014 May; 90 (2014 May; 5; 90):873-81. [Full Text/Abstract]
Charles RC, Hilaire IJ, Mayo-Smith LM, Teng JE, Jerome JG, Franke MF, Saha A, Yu Y, Kováč P, Calderwood SB, Ryan ET, Larocque RC, Almazor CP, Qadri F, Ivers LC, Harris JB. Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti. PLoS Negl Trop Dis. 2014 May; 8 (8; 2014 May; 5):e2828. [Full Text/Abstract]
Zhang J, Zhang K, Gao ZG, Paoletta S, Zhang D, Han GW, Li T, Ma L, Zhang W, Müller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q. Agonist-bound structure of the human P2Y12 receptor. Nature. 2014 May 1; 509 (2014 May 1; 509; 7498):119-122. [Full Text/Abstract]
Nayak A, Chandra G, Hwang I, Kim K, Hou X, Kim HO, Sahu PK, Roy KK, Yoo J, Lee Y, Cui M, Choi S, Moss SM, Phan K, Gao ZG, Ha H, Jacobson KA, Jeong LS. Synthesis and anti-renal fibrosis activity of conformationally locked truncated 2-hexynyl-N(6)-substituted-(N)-methanocarba-nucleosides as A3 adenosine receptor antagonists and partial agonists. J Med Chem. 2014 Feb 27; 57 (4; 2014 Feb 27; 57):1344-54. [Full Text/Abstract]
Alam MM, Bufano MK, Xu P, Kalsy A, Yu Y, Freeman YW, Sultana T, Rashu MR, Desai I, Eckhoff G, Leung DT, Charles RC, LaRocque RC, Harris JB, Clements JD, Calderwood SB, Qadri F, Vann WF, Kováč P, Ryan ET. Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide. PLoS Negl Trop Dis. 2014 Feb; 8 (8; 2; 2014 Feb):e2683. [Full Text/Abstract]
Soliman, S. E.; Kovac, P. Practical Synthesis of Building Blocks for Oligosaccharides Containing the β-D-Galp-(1→3)-β-D-GlcpNAc Motif. Synthesis. 2014; 46 (46; 2014):748-751. [Full Text/Abstract]
Balasubramanian R, Robaye B, Boeynaems JM, Jacobson KA. Enhancement of glucose uptake in mouse skeletal muscle cells and adipocytes by P2Y6 receptor agonists. PLoS One. 2014; 9 (2014; 12; 9):e116203. [Full Text/Abstract]
Englund EA, Zhang N, Appella DH. Cyclopentane peptide nucleic acids. Methods Mol Biol. 2014; 1050 (2014; 1050):13-8. [Full Text/Abstract]
Jacobson KA. Crystal structures of the A2A adenosine receptor and their use in medicinal chemistry. In Silico Pharmacol. 2013 Dec 20; 1 (2013 Dec 20; 1):22. [Full Text/Abstract]
Kruse AC, Ring AM, Manglik A, Hu J, Hu K, Eitel K, Hübner H, Pardon E, Valant C, Sexton PM, Christopoulos A, Felder CC, Gmeiner P, Steyaert J, Weis WI, Garcia KC, Wess J, Kobilka BK. Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature. 2013 Dec 5; 504 (504; 2013 Dec 5; 7478):101-6. [Full Text/Abstract]
Jahouh F, Xu P, Vann WF, Kováč P, Banoub JH. Mapping the glycation sites in the neoglycoconjugate from hexasaccharide antigen of Vibrio cholerae, serotype Ogawa and the recombinant tetanus toxin C-fragment carrier. J Mass Spectrom. 2013 Oct; 48 (2013 Oct; 48; 10):1083-90. [Full Text/Abstract]
Wess J, Nakajima K, Jain S. Novel designer receptors to probe GPCR signaling and physiology. Trends Pharmacol Sci. 2013 Jul; 34 (7; 2013 Jul; 34):385-92. [Full Text/Abstract]
Leung DT, Uddin T, Xu P, Aktar A, Johnson RA, Rahman MA, Alam MM, Bufano MK, Eckhoff G, Wu-Freeman Y, Yu Y, Sultana T, Khanam F, Saha A, Chowdhury F, Khan AI, Charles RC, Larocque RC, Harris JB, Calderwood SB, Kovác P, Qadri F, Ryan ET. Immune responses to the O-specific polysaccharide antigen in children who received a killed oral cholera vaccine compared to responses following natural cholera infection in Bangladesh. Clin Vaccine Immunol. 2013 Jun; 20 (20; 6; 2013 Jun):780-8. [Full Text/Abstract]
Jain S, Ruiz de Azua I, Lu H, White MF, Guettier JM, Wess J. Chronic activation of a designer G(q)-coupled receptor improves β cell function. J Clin Invest. 2013 Apr 1; 123 (2013 Apr 1; 123; 4):1750-62. [Full Text/Abstract]
Micklitsch CM, Oquare BY, Zhao C, Appella DH. Cyclopentane-peptide nucleic acids for qualitative, quantitative, and repetitive detection of nucleic acids. Anal Chem. 2013 Jan 2; 85 (85; 2013 Jan 2; 1):251-7. [Full Text/Abstract]
Johnson RA, Uddin T, Aktar A, Mohasin M, Alam MM, Chowdhury F, Harris JB, LaRocque RC, Bufano MK, Yu Y, Wu-Freeman Y, Leung DT, Sarracino D, Krastins B, Charles RC, Xu P, Kovác P, Calderwood SB, Qadri F, Ryan ET. Comparison of immune responses to the O-specific polysaccharide and lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi adult patients with cholera. Clin Vaccine Immunol. 2012 Nov; 19 (19; 2012 Nov; 11):1712-21. [Full Text/Abstract]
Ruiz de Azua I, Nakajima K, Rossi M, Cui Y, Jou W, Gavrilova O, Wess J. Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo. FASEB J. 2012 Oct; 26 (2012 Oct; 10; 26):4275-86. [Full Text/Abstract]
Tosh DK, Paoletta S, Deflorian F, Phan K, Moss SM, Gao ZG, Jiang X, Jacobson KA. Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity. J Med Chem. 2012 Sep 27; 55 (2012 Sep 27; 55; 18):8075-90. [Full Text/Abstract]
Jacobson KA, Costanzi S. New insights for drug design from the X-ray crystallographic structures of G-protein-coupled receptors. Mol Pharmacol. 2012 Sep; 82 (2012 Sep; 82; 3):361-71. [Full Text/Abstract]
Shahzad-ul-Hussan S, Ghirlando R, Dogo-Isonagie CI, Igarashi Y, Balzarini J, Bewley CA. Characterization and carbohydrate specificity of pradimicin S. J Am Chem Soc. 2012 Aug 1; 134 (30; 2012 Aug 1; 134):12346-9. [Full Text/Abstract]
Sail D, Kováč P. Benzoylated ethyl 1-thioglycosides: direct preparation from per-O-benzoylated sugars. Carbohydr Res. 2012 Aug 1; 357 (2012 Aug 1; 357):47-52. [Full Text/Abstract]
Jahouh F, Saksena R, Kováč P, Banoub J. Revealing the glycation sites in synthetic neoglycoconjugates formed by conjugation of the antigenic monosaccharide hapten of Vibrio cholerae O1, serotype Ogawa with the BSA protein carrier using LC-ESI-QqTOF-MS/MS. J Mass Spectrom. 2012 Jul; 47 (7; 2012 Jul; 47):890-900. [Full Text/Abstract]