The overall goal of the Organic Synthesis shared resource is to provide to Penn State Cancer Institute members chemical compounds that are either not commercially available or that are too cost-prohibitive to allow research to be conducted.
In addition, the shared resource provides radioisotope compounds (3H, 14C, 32P) for pharmacokinetic studies and stable isotope compounds (2H, 15N, 13C) as internal standards for qualitative and quantitative biochemical and metabolomic studies.
The shared resource also provides cancer chemopreventive agents, therapeutic agents and natural products, as well as chemical carcinogens such as tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons and food mutagens.
Sensitive and selective biomarkers of uptake and metabolic activation of carcinogens for the identification of etiologically significant host factors are also provided.
- Seven 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
- Freeze Dry Lyophilizer system (Labconco)
- 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)
- 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 chemopreventive and chemotherapeutic 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-d agonists and antagonists, Sirt1 inhibitors and many more. 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/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 such as separation of enantiomeric mixtures, PK/PD and metabolism studies.
For details on the Organic Synthesis shared resource, contact: