During FY2011, a series of substrates was prepared for biological testing for several diverse projects. These preparations required the development of new methods for construction and purification of the chemical structures required for the assays. The projects included: delivery and testing of new A2A receptor antagonists (publications 2-4);P97 inhibitors which stop endoplasmic reticulum associated degradation (ERAD) without inhibiting ATPase activity (publication 5);and development of a new process for the preparation of topical microbicides against HIV (Publication 1). Biological studies are currently underway to delineate the future directions of the various aspects of these project. The projects collaboratively supported by this research project include: Z01 DK060101-04 -- Targeted disruption the enzymes of O-GlcNAc cycling: Animal models of Disease Z01 DK060102-04 -- Calmodulin-driven Nuclear Trafficking linked to diabetes and insulin signaling Z01 DK060103-04 -- Enzymes of O-GlcNAc cycling linked to type-2 diabetes and neurodegeneration Z01 DK031117-22 -- Development Of Drugs Acting At Adenosine Receptors Z01 EB000001-06 -- New Radiopharmaceuticals and New Paradigms in Positron Emission Tomography Z01 DK036136-04 -- The deubiquitinating inhibitor EerI induces tumor cell apoptosis Z01 DK031143-06 -- Chemically Modified Peptide Nucleic Acids Z01 DK031116-22 -- Development Of P2Y Receptor Ligands Z01 DK031115-26 -- Functionalized Congeners Of Bioactive Compounds

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$395,293
Indirect Cost
City
State
Country
Zip Code
Bhattacharjee, Abesh Kumar; Lang, Lixin; Jacobson, Orit et al. (2011) Striatal adenosine A(2A) receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [(18)F]-MRS5425. Nucl Med Biol 38:897-906
Kumar, T Santhosh; Mishra, Shilpi; Deflorian, Francesca et al. (2011) Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold. Bioorg Med Chem Lett 21:2740-5
Bahde, Robert J; Appella, Daniel H; Trenkle, William C (2011) A one-pot preparation of N-2-mercaptobenzoyl-amino amides. Tetrahedron Lett 52:4103-4105
Shinkre, Bidhan A; Kumar, T Santhosh; Gao, Zhan-Guo et al. (2010) Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists. Bioorg Med Chem Lett 20:5690-4
Wang, Qiuyan; Shinkre, Bidhan A; Lee, Jin-gu et al. (2010) The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group. PLoS One 5:e15479