Synthesis and Screening Facilities

The Small Molecule Synthesis facility at Duke University is a component of the Duke University Center for Chemical Biology and was established to provide synthetic organic chemistry capabilities to the entire University community.

Synthetic services include the preparation of:

• focused small molecule libraries (to ~ 100 compounds)
• milligram to gram quantities of pure small molecules
• hundred gram quantities of materials to support larger scale studies

All materials are fully characterized (NMR, IR, GC/HPLC, MS, combustion) and of guaranteed purity.

The facility has the capability to:

• reproduce literature syntheses,
• develop new synthetic routes, or
• modify/improve on existing literature syntheses.

The Center for Chemical Biology is currently working with the FDA to develop Good Manufacturing Protocols (GMP) synthesis capabilities to support animal studies and phase I/II human trials.

The fully-hooded synthetic Synthesis Facility has access to all routine synthetic equipment, as well as modern multidimensional NMR (to 800 MHz), various mass spectrometry capabilities (EI & CI double focusing high resolution, GC/MS, LC/MS, electrospray, MALDI) and all routine optical spectroscopy.

Small Molecule Synthesis Facility Contacts:

Director: Professor Eric Toone

Professor of Chemistry and Professor of Biochemistry
Duke University
B120 Levine Science Research Center
Durham, NC 27708
Ph (919) 681-3484
Fax (919) 668-5483
toone@chem.duke.edu

Operational Supervisory: Dr. Xin Chen
Assistant Research Professor of Chemistry
B120 Levine Science Research Center
Durham, NC 27710
Ph (919) 684 0237
Fax (919) 668 5483
xin.chen@duke.edu

Various Ph.D. and B.Sc./M.Sc level researchers complete the staffing of the facility

Fees: Fee-for-service basis; charges typically run to $600/day for most routine organic syntheses

Screening Facility

The facility works in close association with the Duke University Screening Facility. This facility, again operated through the Duke University Center for Chemical Biology, assists Duke investigators exploit the opportunities presented by the rapidly advancing state of contemporary chemistry and biology. In parallel with the acquisition of diverse compound libraries, the development of assays directed at molecular targets or cellular processes suitable for screening these libraries is being undertaken. Implementation of such assays on a large scale has been made practical by recent engineering advances in robotics and information processing.

The Facility has two chemical libraries that contain 50,000 unique compounds, which is ideal for “lead compound discovery” opportunities. To efficiently screen this large compound collection, the Screening Facility has two robotic platforms: a Beckman Biomek FX high-throughput system for the actual screening itself and a Beckman Saigan Multimek for routine library maintenance procedures such initial plate setup, mother-daughter plate creation, etc.

To quantify the results from the assays, the Screening Facility has access to microplate readers for UV-vis fluorescence, luminescence, and scintillation spectroscopy. In addition, we will soon have access to a fluorescence microscope with 96/384-well capacity for analysis of cell-based assays using fluorescent protein readouts.

Collaborative Efforts

The Synthesis and Screening Facilities work in close collaboration. Duke investigators bring formatted and tested assays to the screening facility and have access to the diversity library on a cost plus basis. Initial “hits” from the discovery library screen are transferred to the Synthesis Facility for resynthesis and validation. Lead compounds can then be optimized in the Synthesis Facility along any of several vectors (affinity, solubility, membrane penetration, toxicity) through the preparation of focused libraries. Finally, synthesis on scale to support in vitro and in vivo studies is provided.

Eric Toone, PhD DTRI Chemistry and Molecular Therapy Core Anne T. and Robert M. Bass Professor of Chemistry Professor of Biochemistry Dr. Eric Toone studied in Canada, conducting graduate research with Professor Bryan Jones at the University of Toronto on the utility of hydrolytic enzymes in organic synthesis.

Following postdoctoral studies with Professor George Whitesides at Harvard University, Professor Toone began his independent career in the Department of Chemistry at Duke in 1990. He has been a fellow of the Alfred P. Sloan Society, a Camille Dreyfus Teacher-Scholar, and was named the Anne T. and Robert M. Bass Professor of Chemistry in 1998. Professor Toone holds appointments in both the Departments of Chemistry and Biochemistry, and is the Director of the Duke University Center for Chemical Biology. Professor Toone’s research interests surround modern chemical biology, including the use of wild-type and engineered enzymes for organic synthesis, the thermodynamic origin of affinity and selectivity in aqueous association processes, and the chemistry and biology of nitric oxide. Professor Toone has authored over 100 scientific papers and nearly 50 US and international patents. Currently Professor Toone serves as Editor in Chief of Advances in Enzymology and as an Associate Editor of Biopolymers. See http://www.chembio.duke.edu/ for more information.