Chemistry Newsblog

Our last speaker for our Spring Seminar Series is Dr. Blake R. Peterson from Ohio State University.

Dr. Peterson is the chair and a professor in the Division of Medicinal Chemistry and Pharmacognosy, John W. Wolfe Chair in Cancer Research, Co-Leader, OSUCCC Translational Therapeutics Program, and Co-Director, OSUCCC Medicinal Chemistry Shared Resource.

The seminar on Subcellular Targeting for Phenotypic Drug Discovery is at 3:00 pm this Friday, April 9th, via Zoom.

Abstract:
Phenotypic drug discovery represents an important approach for the identification of therapeutics because it does not require extensive knowledge of a specific drug target or mechanism of action. We are using this approach in conjunction with the synthesis of molecular probes that accumulate in specific organelles to discover novel anticancer agents and tool compounds. In this seminar, I will describe the use of this phenotypic discovery / subcellular targeting strategy to identify small molecule anticancer agents. The organelle that we are targeting with these probes is the endoplasmic reticulum (ER), which is defined by an extensive network of intracellular membranes and plays critical roles in the processing of secreted and transmembrane proteins. To deliver small molecules to membranes of this organelle, we synthesized novel fluorinated fluorophores derived from a fluorophore that we previously reported termed Pennsylvania Green. I will describe how these compounds can be used to inhibit a specific protein processing pathway controlled by the ER, and how we built on this molecular platform to create uniquely sensitive sensors of the reactive nitrogen species peroxynitrite, which contributes to immunosuppression in cancer. We further used an optimized peroxynitrite sensor in a phenotypic drug discovery campaign to identify small molecules capable of blocking the production of this reactive species in immune cells prevalent in the tumor microenvironment. This approach could lead to novel small molecule inhibitors and repurposing of existing drugs as therapeutics that help overcome immunosuppression in cancer.

Bio:
Blake Peterson was raised in Reno, Nevada. After receiving a B.S. in Chemistry from the University of Nevada Reno in 1990, he pursued a PhD in Chemistry with Prof. François Diederich at UCLA. During his graduate training, he moved with Prof. Diederich to Switzerland, where he conducted research for two years at the ETH-Zurich. In 1994, he accepted a postdoctoral position with Prof. Gregory Verdine in the Dept. of Chemistry and Chemical Biology at Harvard University as a Damon Runyon / Walter Winchell Cancer Research Foundation Fellow. In 1998, he joined the faculty in the Dept. of Chemistry at Penn State University as an Assistant Professor and was promoted to Associate Professor with tenure in 2004. During this time, he was named a research scholar of the American Cancer Society in 2003 and was the recipient of a Camille Dreyfus Teacher Scholar Award in 2004. In 2008, he joined the faculty of the Department of Medicinal Chemistry at the University of Kansas as Regents Distinguished Professor and was named an Eminent Scholar by the Kansas Biosciences Authority. In 2013, he was elected as a fellow of the American Association for the Advancement of Science (AAAS). In 2019, he joined the faculty of The Ohio State University College of Pharmacy as Professor and Chair of the Division of Medicinal Chemistry and Pharmacognosy. He additionally holds appointments at the Ohio State University Comprehensive Cancer Center as John W. Wolfe Chair in Cancer Research, Co-Leader of the Translational Therapeutics Program, and Co-Director of the Medicinal Chemistry Shared Resource. His current research interests involve the pursuit of new strategies for early-stage anticancer drug discovery.

Our next Chemistry Seminar will be this Friday at 3 p.m. via Zoom.

Dr. Patrick Tomco will be presenting his piece on “Petroleum-derived dissolved organic matter from oil spill cleanup at high latitudes: formation, photo-oxidation, and ecotoxicological effects.”

Dr. Tomco is an Assistant Professor and ASET Lab Coordinator in the Department of Chemistry from the University of Anchorage Alaska.

Abstract:
Oil and gas drilling have been occurring in Alaska since the 1950s, and additional lease sales are planned for Cook Inlet and the Beaufort Sea. As regions in the Arctic become ice-free, offshore drilling in that area is expected to increase. As petroleum development increases, so does the risk of another major oil spill. Oil spills can have a devastating effect on the marine environment, and dispersants, chemical herders, and in-situ burning are supposed to mitigate that effect. Despite some of the benefits, this technique appears to have on oil spill mitigation, opinions on the utilization of these strategies are polarized, and the issue requires careful consideration and study. This talk will focus on several recent investigations aimed at characterizing hydrocarbon-derived dissolved organic matter (DOMHC), photochemical products of DOMHC, photo-modified DOMHC bioavailability, and resulting toxicity potential of DOMHC to Arctic marine aquatic life (mussels, Mytilus trossulus). Characterization methods include Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS), fluorescence excitation emission matrices (EEMs), toxicity biomarkers, 16S rRNA sequencing, and NMR-based metabolomics. 

Bio:
Patrick Tomco, Ph.D is an Assistant Professor of Chemistry at the University of Alaska Anchorage, Chair of the Alaska ACS Local Section, and manager of the Applied Science Engineering and Technology (ASET) laboratory.

There will be a Chemistry Seminar at 3 p.m. Friday, March 26th via Zoom.

Dr. Clint P. Aichele will present “Biomimetic Hydrogels for Protein Delivery, Stabilization, and Immobilization.”

Aichele is an Associate Professor and Lew Ward Faculty Fellow in the School of Chemical Engineering at Oklahoma State University.

Abstract: Proteins are incredibly useful in medicine and industrial chemistry. Many of the most recent breakthroughs in cancer therapy are based on monoclonal antibody treatments. Yet, there are major difficulties that can act as deterrents in developments of such therapies. Sustained subcutaneous, oral or pulmonary deliveries of such therapeutics are limited by the poor stability, short half-life, and non-specific interactions between the therapeutic biomolecules (e.g. antibody) and the delivery vehicle. Similarly, usage of proteins as enzymes in processes is limited by poor stability, short half-life, and difficulties with reusability. With growing usage of proteins as pharmaceuticals and biocatalysts, and apparent shortcomings in both fields, there is a growing need to design materials that are protein compatible and can improve protein stability. The key to successfully utilizing proteins as therapeutics, biocatalysts or biosensors is to maintain their conformation and function. There is emerging evidence that biomimetic, biocompatible zwitterionic polymers can prevent non-specific interactions within proteins systems and increase protein stability. For the purpose of protein delivery, a biodegradable zwitterionic poly(carboxybetaine) based microscale hydrogel (microgel) was synthesized. The resulting microgels were characterized via FTIR, diffusion NMR, SANS, and cell culture studies. We examined a novel post-fabrication technique that resulted in effective loading of IgG in the microgels. The released antibodies (especially from the high crosslinked microgels) proved to be completely active and able to bind with antibody receptors. Furthermore, for the purpose of protein immobilization, reaction a scheme was developed and studied for covalent immobilization of the protein (α-chymotrypsin) (ChT) within the zwitterionic microscale hydrogels. This research paves the way for designing protein delivery vectors as well as fabrication of enzyme immobilized materials with extended enzyme lifetime and activity.

Bio: Dr. Clint P. Aichele is an Associate Professor and Lew Ward Faculty Fellow in the School of Chemical Engineering at Oklahoma State University. Dr. Aichele’s research is in the area of colloids and interfacial phenomena with specific applications in gas/liquid separation, emulsions, enhanced oil recovery, distillation, and flow assurance. His work specifically focuses on engineering interfaces to solve separation challenges in complex fluids. Dr. Aichele received his B.S. in Chemical Engineering from OSU in 2004 and Ph.D. from Rice University in 2009. Dr. Aichele worked at ConocoPhillips as a Research Engineer for 3 years in the CO2 Capture and Avoidance group prior to joining the faculty at Oklahoma State University.