Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Botulinum neurotoxin (BoNT), a protein that is produced by Clostridium botulinum, is the most poisonous protein in the world. The active site of BoNT includes a zinc endopeptidase, whose structure has been elucidated by x-ray crystallography. Herein we propose to synthesize a library of inhibitors for the zinc endopeptidase subunit. The key structural element of these inhibitors is a 2- or 3-aryl indole. These moieties will be synthesized using oxidative coupling technology that has recently been developed in the PI's laboratory. Biological testing of the inhibitors will be performed in the laboratory of a collaborator at the Botulism Research Center at the University of Massachusetts-Dartmouth.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
2P20RR016457-09
Application #
7960154
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2009-05-04
Project End
2010-04-30
Budget Start
2009-05-04
Budget End
2010-04-30
Support Year
9
Fiscal Year
2009
Total Cost
$21,222
Indirect Cost

  Institution

Name
University of Rhode Island
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881

  Publications

Taylor, David L; Calabrese, Nicholas M (2018) Mercury content of blue crabs (Callinectes sapidus) from southern New England coastal habitats: Contamination in an emergent fishery and risks to human consumers. Mar Pollut Bull 126:166-178
Chen, Xiaodi; Hovanesian, Virginia; Naqvi, Syed et al. (2018) Systemic infusions of anti-interleukin-1? neutralizing antibodies reduce short-term brain injury after cerebral ischemia in the ovine fetus. Brain Behav Immun 67:24-35
Paquin, Karissa L; Howlett, Niall G (2018) Understanding the Histone DNA Repair Code: H4K20me2 Makes Its Mark. Mol Cancer Res 16:1335-1345
Vierra, David A; Garzon, Jada L; Rego, Meghan A et al. (2017) Modulation of the Fanconi anemia pathway via chemically induced changes in chromatin structure. Oncotarget 8:76443-76457
Wan, Jerry; Lin, Fuquan; Zhang, Wei et al. (2017) Novel approaches to vitiligo treatment via modulation of mTOR and NF-?B pathways in human skin melanocytes. Int J Biol Sci 13:391-400
Taylor, David L; Williamson, Patrick R (2017) Mercury contamination in Southern New England coastal fisheries and dietary habits of recreational anglers and their families: Implications to human health and issuance of consumption advisories. Mar Pollut Bull 114:144-156
Hahn, Mark E; Karchner, Sibel I; Merson, Rebeka R (2017) Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution. Curr Opin Toxicol 2:58-71
Preiss, Matthew R; Cournoyer, Eily; Paquin, Karissa L et al. (2017) Tuning the Multifunctionality of Iron Oxide Nanoparticles Using Self-Assembled Mixed Lipid Layers. Bioconjug Chem 28:2729-2736
Tiwari, Rakesh K; Brown, Alex; Sadeghiani, Neda et al. (2017) Design, Synthesis, and Evaluation of Dasatinib-Amino Acid and Dasatinib-Fatty Acid Conjugates as Protein Tyrosine Kinase Inhibitors. ChemMedChem 12:86-99
Shimpi, Prajakta C; More, Vijay R; Paranjpe, Maneesha et al. (2017) Hepatic Lipid Accumulation and Nrf2 Expression following Perinatal and Peripubertal Exposure to Bisphenol A in a Mouse Model of Nonalcoholic Liver Disease. Environ Health Perspect 125:087005

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