The mission of the Organic Synthesis Shared Resource (OSSR) is to advance the scientific impact and excellence of Penn State Cancer Institute (PSCI) investigators by synthesizing and providing chemical agents that are either not commercially available or cost-prohibitive, to facilitate ongoing cancer research. The OSSR also assists in the efforts towards discovering novel agents for the treatment and prevention of cancer.
The research support activities of the OSSR encompass the development and synthesis of anticancer agents, chemical carcinogens, their detoxification products, reactive species of metabolic activation and DNA adducts formed with such species. OSSR activities also include the identification and synthesis of biomarkers of uptake and activation of environmental carcinogens that require deuterated, tritiated, and 14C-labeled isotopes.
- Six high-pressure liquid chromatography instruments with a variety of detectors such as UV, β-flow radioactivity, photodiode array (PDA), fluorescence and evaporative light scattering (ELS)
- Temperature-sensitive probes (J-KEM Scientific)
- Excella E24 Incubator Shaker (New Brunswick Scientific)
- Glove box for inert atmosphere-sensitive reaction
- Discover microwave reactor (CEM)
- Photochemical immersion well reactor with a mercury-vapor lamp
- Legend T Plus benchtop centrifuge (Thermo Scientific)
- Expression-S benchtop compact mass spectrometer (Advion)
- CE 2014 UV Spectrophotometer (CECIL)
- Parallel synthesizer
- Isolera flash chromatography system
- Access to 500 and 600 MHz NMR spectrophotometers, and several mass spectrometers through Penn State College of Medicine's core facilities
- Expertise and consultation in the area of chemical synthesis and design of small molecules to Penn State Cancer Institute members
- Counsel on the custom synthesis of essentially any organic-based compound and developing improved synthetic routes
- Development of scale-up protocols for pure materials for pre-clinical investigations (the shared resource is capable of handling the synthesis of organic molecules from mg to kg scale)
- Facilitation of collaborations among molecular chemists, biologists, structural biologists, pharmacologists and clinicians
- Synthesis of anticancer agents: Synthesis of both naturally occurring and synthetic chemicals, including kinase inhibitors such as inhibitors of PI3K/Akt, Rho kinase, sphingosine kinase; topoisomerase-II inhibitors, Ahr receptor agonists, PPAR-β/δ agonists and antagonists, Sirt1 inhibitors, aldehyde dehydrogenase inhibitors, protein phosphatase A (PPA) activators and other drug-like small molecules. The shared resource is also extensively involved in the optimization of lead compounds identified by researchers from screening of chemical libraries.
- Synthesis of chemical carcinogens and their metabolites: The shared resource conducts synthesis of chemical carcinogens such as polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, environmental and nutritional carcinogens, their proximate and ultimate metabolites, detoxification products, DNA adducts and biomarkers. These compounds are particularly essential for scientists investigating mechanisms of carcinogenesis and chemoprevention.
- Synthesis of radio- and isotope-labeled compounds: The shared resource has the expertise and facilities to synthesize radioisotope and stable isotope labeled small molecules, including chemopreventive and chemotherapeutic agents and chemical carcinogens. These include deuterated analogs used as internal standards and 3H- and 14C-labeled isotopes for quantitative work.
- Analytical techniques: The shared resource also helps Cancer Institute investigators with development of analytical techniques required for separation of enantiomeric mixtures, analyses of samples from PK/PD and metabolism studies and many more.
For details on the Organic Synthesis shared resource, contact: