Organic Synthesis Core
The overall goal of the Organic Synthesis Core (OSC) is to provide to the PSHCI members, the chemical compounds that are not commercially available or too cost-prohibitive to undertake the research. In addition, OSC also provides radio-labeled (3H, 14C, 32P) compounds for pharmacokinetic studies and isotope-labeled (2H, 15N, 13C) compounds as internal standard for qualitative and quantitative biochemical and metabolomic studies. OSC 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. The facility is located on the seventh floor of Crescent Building in close proximity of the Penn State Hershey Cancer Institute; occupying a total space of 2050 sq. ft. At present, about 1700 sq. ft. is designated for the synthesis of intermediates, carcinogens and chemopreventive/chemotherapeutic agents with the remaining 350 sq. ft. for the synthesis of radio-labeled compounds. The facility is also equipped with several high-pressure liquid chromatography sets including instruments equipped with a variety of detectors such as beta-flow radioactivity, photodiode array (PDA), fluorescence, and evaporative light scattering (ELS) which is useful for detecting semi- or non-volatile compounds with little or no UV absorbance. The OSC was initially organized within the Institute of Cancer Prevention (IFCP) in Valhalla, New York. Importantly, through NCI Chemical Repository and through OSC we have provided chemical agents, standards and markers to the research community throughout USA and all around the world for many years now.
The general capabilities of the core include:
- Provide expertise, consultations, and experience in the area of chemical synthesis and design of small molecules to the PSHCI members.
- Provide counsel on the custom synthesis of essentially any organic-based compound and developing improved synthetic routes.
- Provide scale-up protocols for pure materials for pre-clinical investigations.
- Facilitate collaborations among molecular chemists, biologists, structural biologists, pharmacologists and clinicians.
The OSC is capable of handling the synthesis of all structural classes of small to large organic molecules from mg to kg scale. State-of-the-art organic synthesis and modern synthetic methodologies are used for the efficient construction of molecular agents and ligands in modern, well-equipped laboratories to supply highly purified compounds. The Core provides an affordable means and knowledge to access chemical technology that cannot be supported by other individual labs. The intellectual and technical resources of the OSC can assist researchers in designing and conducting the proper experimentation, selecting suitable methods of analysis, preparing samples as well as, in most cases, analyzing them on premises.
The types of services provided include:
- Synthesis of chemopreventive and chemotherapeutic agents: Synthesis of both naturally occurring and synthetic chemicals e.g. 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 Core is also involved extensively in the optimization of lead compounds identified by researchers from screening of chemical libraries.
- Synthesis of chemical carcinogens and their metabolites: The core conducts synthesis of chemical carcinogens such as polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), environmental and nutritional carcinogens, their proximate and ultimate metabolites, detoxification products, DNA adducts, and biomarkers. These compounds are essential particularly for scientists investigating mechanisms of carcinogenesis and chemoprevention.
- Synthesis of radio- and isotope-labeled compounds: The Core has the expertise and facilities to synthesize radio- and isotope- labeled small molecules including chemopreventive/ chemotherapeutic agents, and chemical carcinogens. These include deuterated analogs used as internal standards and tritiated as well as 14C-labeled isotopes for quantitative work.
- Analytical techniques: The Core also helps PSHCI investigators with development of analytical techniques such as separation of enantiomeric mixtures, PK/PD and metabolism studies.