U.S. Department of Health and Human Services

Laboratory of Bioorganic Chemistry

Kenneth A. Jacobson, Ph.D., Chief

​Research Images

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TitleDescriptionImage
Molecular models of four distinct dimeric arrangements of the M3 muscarinic receptorThe structures shown here represent four distinct low-energy M3 muscarinic receptor dimers that are compatible with experimental BRET data (McMillin SM, et al. J. Biol. Chem. 286, 28584-8, 2011).Enlarge
High-resolution X-ray structure of the M3 muscarinic receptor (M3R)(A) Overall structure of the M3R bound to tiotropium, a muscarinic antagonist used for the treatment of chronic obstructive pulmonary disease and (B) an extracellular view of the tiotropium binding site (Kruse AC, et al. Nature 482, 552-6, 2012).Enlarge
Schematic representation of CNO-sensitive designer GPCRs (DREADDs)All depicted DREADDs contain the Y3.33C and A5.46G point mutations in TM3 and TM5, respectively (indicated by the red 'x marks'). The resulting designer receptors are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor agonist, but can be activated by CNO with high potency and efficacy. CNO is a pharmacologically inactive metabolite of clozapine. Depicted are (B) DREADDs differing in their G protein coupling properties (Armbruster BN, et al. Proc. Natl. Acad. Sci. U.S.A. 104, 5163-8, 2007; Guettier JM, et al. Proc. Natl. Acad. Sci. U.S.A. 106, 19197-19202, 2009) and (C) the structure of an arrestin-biased DREADD (Nakajima KI and Wess J. Mol. Pharmacol. 82, 575-82, 2012).Enlarge
Wess Photo Lab Members(From left to right): Kelly Hu, Yinghong Cui, Derek Bone, Sally McMillin, Shalini Jain, Jürgen Wess, Mario Rossi, Ken-ichiro Nakajima, Wataru Sakamoto, and Jianxin HuEnlarge
Hexasaccharide conjugate (Hexa-rTT-Hc)Conjugate construct (vaccine) made from the Antigen and Carrier by squaric acid chemistry of conjugation, utilizing the sole amino group in the Spacer and amino group in the L-lysine residues present in the carrier.Enlarge
Multivalent conjugate (Multivalent)Bivalent conjugate construct (vaccine) made from Antigens A and B and Carrier by squaric acid chemistry of conjugation, utilizing the sole amino group in each Spacer and amino group in the L-lysine residues present in the carrier.Enlarge
O-PS-core-rTT-Hc conjugate (O-PS-core-rTT-Hc)Conjugate construct (vaccine) made from the Antigen and Carrier by squaric acid chemistry of conjugation, utilizing the sole amino group of D-glucosamine in the core and amino group in the L-lysine residues present in the carrier.Enlarge
Model of the monoclonal anti Vibrio cholerae O1, serotype Ogawa antibody–O-SP complexThis image depicts a model based on the X-ray structure of the Fab crystalline complex, with synthetic disaccharide that mimics terminus of bacterial O-PS. Individual perosamine residues (various colors) are shown along with the light (light blue) and heavy chains (dark blue) of the Ab-variable domains, and the 2-O-methyl group-interface center (yellow). Disaccharide synthesis from Section on Carbohydrates, LBC; crystallography performed at Institute Pasterur, Paris, France; taken from Villeneuve et al., PNAS, Vol. 97 (2000) 8433–8438Enlarge
Engineering of Selective Ligands for Mechanistic ProbingEngineering of selective ligands for mechanistic probing and therapeutic modulation of adenosine and P2Y nucleotide receptors.Enlarge
The newly determined structure of the A2A receptor for adenosineThe newly determined structure of the A2A receptor for adenosine is shown surrounding its synthetic agonist.Enlarge
Molecular model of a homodimeric A2A adenosine receptorDepicted is a molecular model of a homodimeric A2A adenosine receptor containing a bound conjugate of a PAMAM (polyamidoamine) dendrimer and an A2A agonist, CGS21680. In this model, the multivalent dendrimer conjugate is able to bridge both binding sites of the dimeric receptor. Bioorg. Med. Chem. Lett., 2008, 18:4312-4315Enlarge
Comparison of locked ring ribose analogues of nucleotides binding at adenosine and P2Y receptorsDepicted is a methanocarba ring as a ribose modifi cation in ligands of G protein-coupled purine and pyrimidine receptors. Source: Tosh, D.K., Jacobson, K.A. Methanocarba ring as a ribose modification in ligands of G protein-coupled purine and pyrimidine receptors: Synthetic approaches. Med. Chem. Comm., 2013, 4:619-630Enlarge
Modern mass specThis is a diagram of a modern mass spec. These are benchtop units with greatly increased capabilities, sensitivities, and resolution than the instruments that were in service just 5 years ago.Enlarge
GeLC-MSThis a workflow diagram depicting how we identify the protein components of complex samples.Enlarge
LC/MSThe bottom trace is an LC/MS of a biological extract and the top traces show the MS spectrum of one of the LC peaks.Enlarge