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Dr. John 'Jay' Schneekloth


Dr. John 'Jay' Schneekloth
Chemical Genetics
301-228-4620

Research Summary

Small Molecule Probes of Ubiquitin-like Signaling
The dynamic modulation of protein posttranslational modifications is a major regulatory mechanism in cellular homeostasis. Greater than 90% of the proteome is regulated by modification with small protein tags such as ubiquitin or ubiquitin-like molecules. The posttranslational ligation or cleavage of these tags affects critical events such as gene transcription, subcellular localization, protein degradation, and many others. It is not surprising to note that disruption of these pathways is associated with a large number of disease states, including a many cancers. A major goal of the lab is to utilize synthetic chemistry to generate new small molecule probes of specific enzymes within ubiquitin-like signaling pathways, including druglike enzyme inhibitors as well as activity based probes.

Inhibiting Protein-Protein Interactions With Oligomeric Molecules
A major area of interest in medicinal chemistry is the inhibition of protein-protein interactions with small synthetic molecules. Many protein-protein interactions are of high therapeutic interest, but are classically considered 'undruggable'. Strategies to disrupt these interactions (for example, receptor-ligand interactions on cell surfaces) will provide new opportunities for the treatment of cancer, HIV/AIDS, and many other diseases. This area of the lab focuses on developing new oligomeric small molecules that perturb disease-relevant protein-protein interactions, and understanding how the structure of these molecules allows them to interact with protein surfaces.

Publications
1 - 5 of 17 results

1)  Kim YS, Keyser SG, Schneekloth JS.
Synthesis of 2",3",4"-trihydroxyflavone (2-D08), an inhibitor of protein sumoylation.
Bioorg. Med. Chem. Lett. 2014. [Journal]

2)  Kim YS, Nagy K, Keyser S, Schneekloth JS.
An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.
Chem. Biol. 20: 604-13, 2013. [Journal]

3)  Kim J, Schneekloth J, Sorensen E.
A chemical synthesis of 11-methoxy mitragynine pseudoindoxy featuring the interrupted Ugi reaction.
Chem. Sci. 3: 2849-52, 2012. [Journal]

4)  Kim J, Schneekloth JS, Sorensen EJ.
A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the interrupted Ugi reaction.
Chem Sci. 3: 2849-2852, 2012. [Journal]

5)  Noblin DJ, Page CM, Tae HS, Gareiss PC, Schneekloth JS, Crews CM.
A HaloTag-based Small Molecule Microarray Screening Methodology with Increased Sensitivity and Multiplex Capabilities.
ACS Chem. Biol. 7: 2055-63, 2012. [Journal]

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