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.

Grundmann M, Merten N, Malfacini D, Inoue A, Preis P, Simon K, Rüttiger N, Ziegler N, Benkel T, Schmitt NK, Ishida S, Müller I, Reher R, Kawakami K, Inoue A, Rick U, Kühl T, Imhof D, Aoki J, König GM, Hoffmann C, Gomeza J, Wess J, Kostenis E. Lack of beta-arrestin signaling in the absence of active G proteins. Nat Commun. 2018 Jan 23; 9 (2018 Jan 23; 9; 1):341. [Full Text/Abstract]
Rossi M, Zhu L, McMillin SM, Pydi SP, Jain S, Wang L, Cui Y, Lee RJ, Cohen AH, Kaneto H, Birnbaum MJ, Ma Y, Rotman Y, Liu J, Cyphert TJ, Finkel T, McGuinness OP, Wess J. Hepatic Gi signaling regulates whole-body glucose homeostasis. J Clin Invest. 2018 Jan 16; 128 (128; 2; 2018 Jan 16):746-759. [Full Text/Abstract]
Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. Nat Commun. 2017 Feb 1; 8 (2017 Feb 1; 8):14295. [Full Text/Abstract]
Hartman TL, Yang L, Helfrick AN, Hassink M, Shank NI, George Rosenker K, Scerba MT, Saha M, Hughes E, Wang AQ, Xu X, Gupta P, Buckheit RW Jr, Appella DH. Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus. Antiviral Res. 2016 Aug 25; 134 (134; 2016 Aug 25):216-225. [Full Text/Abstract]
Wess J. Use of Designer G Protein-Coupled Receptors to Dissect Metabolic Pathways. Trends Endocrinol Metab. 2016 Jul 2; 27 (27; 9; 2016 Jul 2):600-3. [Full Text/Abstract]
Mason RD, Welles HC, Adams C, Chakrabarti BK, Gorman J, Zhou T, Nguyen R, O'Dell S, Lusvarghi S, Bewley CA, Li H, Shaw GM, Sheng Z, Shapiro L, Wyatt R, Kwong PD, Mascola JR, Roederer M. Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog. 2016 Apr; 12 (2016 Apr; 4; 12):e1005537. [Full Text/Abstract]
Dogo-Isonagie C, Lee SL, Lohith K, Liu H, Mandadapu SR, Lusvarghi S, O'Connor RD, Bewley CA. Design and synthesis of small molecule-sulfotyrosine mimetics that inhibit HIV-1 entry. Bioorg Med Chem. 2016 Mar 3; 24 (8; 24; 2016 Mar 3):1718-28. [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]
Nakajima K, Cui Z, Li C, Meister J, Cui Y, Fu O, Smith AS, Jain S, Lowell BB, Krashes MJ, Wess J. Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake. Nat Commun. 2016 Jan 8; 7 (2016 Jan 8; 7):10268. [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]
Gupta P, Rastede EE, Appella DH. Multivalent (L)Kγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes. Bioorg Med Chem Lett. 2015 Jul 29; 25 (25; 2015 Jul 29; 21):4757-60. [Full Text/Abstract]
Ugaonkar SR, Clark JT, English LB, Johnson TJ, Buckheit KW, Bahde RJ, Appella DH, Buckheit RW Jr, Kiser PF. An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission. J Pharm Sci. 2015 Jul 6; 104 (104; 2015 Jul 6; 10):3426-39. [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 Koninck 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]
Dix AV, Conroy JL, George Rosenker KM, Sibley DR, Appella DH. PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor. ACS Med Chem Lett. 2015 Apr 9; 6 (6; 4; 2015 Apr 9):425-9. [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]
Lusvarghi S, Ghirlando R, Wong CH, Bewley CA. Glycopeptide mimetics recapitulate high-mannose-type oligosaccharide binding and function. Angew Chem Int Ed Engl. 2015 Mar 16; 54 (2015 Mar 16; 19; 54):5603-8. [Full Text/Abstract]
Acharya P, Lusvarghi S, Bewley CA, Kwong PD. HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets. 2015 Feb 27; 19 (6; 19; 2015 Feb 27):1-19. [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]
Gaynutdinov TI, Englund EA, Appella DH, Onyshchenko MI, Neumann RD, Panyutin IG. G-quadruplex formation between G-rich PNA and homologous sequences in oligonucleotides and supercoiled plasmid DNA. Nucleic Acid Ther. 2015 Feb 4; 25 (25; 2; 2015 Feb 4):78-84. [Full Text/Abstract]
Sastry M, Bewley CA, Kwong PD. Effective isotope labeling of proteins in a mammalian expression system. Methods Enzymol. 2015; 565 (565; 2015):289-307. [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]
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]
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]
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]
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]
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]
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 Dec 30; 9 (12; 9; 2014 Dec 30):e116203. [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]
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]