Research in the Stockdill group is focused on the design of elegant and efficient strategies for the synthesis of complex natural products and for the synthesis and manipulation of proteins and related structures. Through these efforts, we explore chemical reactivity and develop new reaction methods. An overarching theme in the lab is to capitalize on the insights gained in each of the major synthetic areas to inspire and enable novel chemistry in the other.
Synthesis, Manipulation, and Biological Evaluation of Proteins and Mini-Proteins
While small molecule natural products are advantageous drug targets, owing to their stability, relative accessibility, and rigidity, peptide and protein-derived treatments offer unique benefits including their high modularity, exquisite selectivity for their cellular targets, and generally favorable toxicity profiles. Our research in this area addresses serious challenges in the synthetic accessibility of these biomolecules. Synthetic analogs of medically important proteins will be generated to modify their selectivity, stability and pharmacodynamics.
Strategies for the synthesis and folding of disulfide rich proteins
The cysteine knot motif is found in many proteins. This motif can present significant challenges during the folding step of the de novo synthesis of complex protein-derived targets. We are very interested in pursuing new strategies to control this process, as well as in studying the biological activities of our synthetic targets.
Complex natural products as a driving force for the discovery of novel methods
Natural products have served as inspirational targets for synthetic chemists for decades, with structural challenges driving the development of novel methods for the construction of C–C, C–N, and C–O bonds. Meanwhile, they have also been the most consistently successful source of lead targets for pharmaceutical development over the last half-century. However, many promising targets are neglected due to their apparent complexity. Our lab focuses on developing rapid, convergent, and innovative approaches to these challenging structures. Meanwhile, we utilize these architectures as inspirational platforms for the development of novel reaction methods.
Synthesis of polycyclic alkaloids
Our lab is particularly interested in polycyclic alkaloids. These compounds exhibit a range of fascinating biological activities from anti-cancer agents to antibiotics. Once synthetic studies are completed, the synthetic intermediates, targets, and analogs will be tested for biological activity. We will then embark on studies to determine the mechanism of action of these compounds in an effort to not only provide novel potential pharmaceuticals, but also to shed light on the biological pathways involved in particular disease states.
reactions of N-centered radicals
In the context of our synthetic efforts, we have become intrigued by the unusual reactivity profile of aminyl radicals. We are working to elucidate the parameters within which these species function best, in order to improve their utility to the synthetic community.
Exploiting Organic Synthesis to Develop Novel Analytical Tools
Organic chemistry is an enabling science. We capitalize on our experience with complex small molecule and peptide synthesis, combined with an understanding of fundamental physical properties of molecules, to design, synthesize, and then employ novel structures for the detection of important analytes. This work is a collaborative venture with the Hashemi Lab at U. South Carolina.
COVALENT FUNCTIONALIZATION OF CARBON-FIBER MICROELECTRODES
Our lab has partnered with the Hashemi Lab to design a general strategy for the covalent functionalization of carbon-fiber microelectrodes. With this platform for CFM modification in hand, we are actively pursuing the development of novel sensors for a variety of applications ranging from trace metal detection in environmental systems to probing challenging biological pathways.
Funding
Research in the Stockdill Lab has been funded by the following agencies. We are grateful for their support:
2019–2023, R01 GM129475
2012–2016, Pathway to Independence Award to JLS, R00-GM097095, Minority Supplement Award #: R00-GM097095-S1
2019–2021, LRAP Grant to JLS
2019, Pharmaceutical Roundtable Grant to JLS
2018, Pharmaceutical Roundtable Grant to JLS
2015–2021, CAREER Award to JLS – Award #1554752
Startup Funds to JLS, Rumble-Schaap Fellowship to TDK, CAA & HSS, A. Paul Schaap Distinguished Graduate Fellowship to CAA, Knoller Fellowship to HYS, President’s Research Enhancement funds to JLS, UROP Fellowship to STJ
Internships
The following companies have provided students in the Stockdill Lab with exciting internship opportunities. Thank you!
Dow AgroSciences – Summer Internship for GJR
Boehringer Ingelheim – Summer Internships for CAA & HSS