The Synthesis Core engages in the synthesis of non-commercial agents, hit/lead discovery/development chemistries, medicinal chemistry and/or the modification (e.g., using suitable reactive tags, isotopes, fluorophores) of bioactive probes, drugs or natural products for target identification studies (in conjunction with the UK Proteomics Core). Small molecule hit/lead discovery and development synthetic projects also commonly rely on computational models/ADMET (Computational Core) and evaluative studies conducted by the Translational Core. The Synthesis Core is an affiliate of the UK COBRE for Molecular Medicine and operates under the directorship of Professor Tom Prisinzano with a current staff of three Ph.D. level chemists.
CPRI Synthesis Core
Hit/Lead Optimization
- Synthesis/design consultation
- Synthesis of 10s to 100s of analogs for evaluative assays
De Novo Synthesis
- Synthesis/design consultation
- Synthesis of target molecules based upon computational and/or biochemical models
Probe Synthesis
- Synthesis/design consultation
- Synthesis of target probes based on existing SAR
- Assistance with pull-down assays (w/UK Proteomics Core)
Scale-up Synthesis of Select Agents
- Production of select test agents (≤250 mgs) via fermentation or synthesis
Representative Publications
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Zhang Y, Ye Q, Ponomareva LV, Cao Y, Liu Y, Cui Z, Van Lanen SG, Voss SR, She QB, Thorson JS (2019). Total synthesis of griseusins and elucidation of the griseusin mechanism of action. Chemical Science 10:7641–7648. PMCID: PMC6755659
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Fiandalo MV, Stocking JJ, Pop EA, Wilton JH, Mantione KM, Li Y, Attwood KM, Azabdaftari G, Wu Y, Watt DS, Wilson EM, Mohler JL (2018). Inhibition of dihydrotestosterone synthesis in prostate cancer by combined frontdoor and backdoor pathway blockade. Oncotarget 9(13):11227-11242. PMCID: PMC5834294
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Burikhanov R, Hebbar N, Noothi SK, Shukla N, Sledziona J, Araujo N, Kudrimoti M, Wang QJ, Watt DS, Welch DR, Maranchie J, Harada A, Rangnekar VM (2017). Chloroquine-inducible Par-4 secretion is essential for tumor cell apoptosis and inhibition of metastasis. Cell Reports 18(2):508-519. PMCID: PMC5264245
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Sviripa VM, Burikhanov R, Obiero JM, Yuan Y, Nickell JR, Dwoskin LP, Zhan CG, Liu C, Tsodikov OV, Rangnekar VM, Watt DS (2016). Par-4 secretion: Stoichiometry of 3-arylquinoline binding to vimentin. Organic & Biomolecular Chemistry 14(1):74-84. PMCID: PMC4681656
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Zhang Y, Ye Q, Wang X, She QB, Thorson JS (2015). A divergent enantioselective strategy for the synthesis of griseusins. Angewandte Chemie International Edition 54(38):11219-11222. PMCID: PMC4565752
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Burikhanov R, Sviripa VM, Hebbar N, Zhang W, Layton WJ, Hamza A, Zhan CG, Watt DS, Liu C Rangnekar VM (2014). Arylquins targets vimentin to trigger Par-4 secretion for tumor cell apoptosis. Nature Chemical Biology 10(11):924-926. PMC4201913
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Zhang Y, Wang X, Sunkara M, Ye Q, Ponomareva LV, She QB, Morris AJ, Thorson JS (2013). A diastereoselective oxa-Pictet-Spengler-based strategy for (+)-frenolicin B and epi-(+)-frenolicin B synthesis. Organic Letters 15(21):5566-5569. PMCID: PMC3877857
Inquiries
The Synthesis Core welcomes inquiries from UK investigators with an interest in the application of organic synthesis, medicinal chemistry, and/or chemical biology approaches to facilitate on-going or emerging research projects. For more information and to request services, please contact us.
Funding Acknowledgment Statement
This work was supported by the Center for Pharmaceutical Research and Innovation (CPRI, NIH P20 GM130456) and the National Center for Advancing Translational Sciences (UL1 TR001998).
We wish to remember and honor those who inhabited this Commonwealth before the arrival of the Europeans. Briefly occupying these lands were the Osage, Wyndott tribe, and Miami peoples. The Adena and Hopewell peoples, who are recognized by the naming of the time period in which they resided here, were here more permanently. Some of their mounds remain in the Lexington area, including at UK’s Adena Park.
In more recent years, the Cherokee occupied southeast Kentucky, the Yuchi southwest Kentucky, the Chickasaw extreme western Kentucky and the Shawnee central Kentucky including what is now the city of Lexington. The Shawnee left when colonization pushed through the Appalachian Mountains. Lower Shawnee Town ceremonial grounds are still visible in Greenup County.
We honor the first inhabitants who were here, respect their culture, and acknowledge the presence of their descendants who are here today in all walks of life including fellow pharmacists and healthcare professionals.