Duke University | Chemical Biology Program

Enabling small molecule approaches to biological discovery.

Duke University Small Molecule Synthesis Facility

The Small Molecule Synthesis facility at Duke University was established as a component of the Duke University Center for Chemical Biology in 2003 to provide synthetic organic chemistry capabilities to the entire University community. The Center is located in the Levine Science Research Center, and occupies modern fully hooded synthetic space. The 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) all routine optical spectroscopy, and small molecule diffractometers. The facility Director is Professor Eric Toone, of the Department of Chemistry.

Day-to-day operation of the facility is supervised by Dr. David Gooden. Dr. Gooden has nearly 15 years of academic synthetic experience, and has authored a number of papers and patents. Various Ph.D. researchers complete the staffing of the facility. This group of researchers has extensive expertise both in the execution of synthetic routes and in the planning and execution of medicinal chemistry campaigns, including hit-to-lead and preclinical development services. The Facility has also developed relationships with commercial CROs in North American, China and India: Facility staff work with individual researchers to ensure rapid and cost-efficient access to chemistry support for larger projects and/or shorter timelines. Facility staff can also broker access to a broad range of preclinical chemistry support, including ADME, toxicology and formulation support, in both domestic and foreign settings. Our goal is to make such arrangements completely transparent to the researcher, facilitating rapid and efficient translation from bench top discovery to IND/first in man studies.

The Center operates on a fee-for-service basis, and charges typically run to roughly $800/day for most routine organic syntheses. A range of synthetic services are offered, including the preparation of focused small molecule libraries (to ~ 100 compounds), the preparation of milligram to gram quantities of pure small molecules, including , and the preparation of 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 is currently working to develop GMP synthesis capabilities to support both animal and phase I/II human trials.

The synthesis facility offers training in the discipline of organic synthesis for researchers who have significant synthetic needs and wish to bring the expertise into their own labs. Two fully equipped synthetic bays are available for graduate students or post-doctoral researchers to conduct their own synthetic work, utilizing the guidance of facility staff. Under this arrangement faculty provide only consumable reagents and starting materials, and pay a nominal fee to cover the time of facility staff.

Duke Chemical Biology Faculty

Staff of the Small Molecule Synthesis Facility. From left: Dr. Ramesh GopalSwami, Dr. Michael Gorczynski, Dr. Xin Chen and Dr. David Gooden.

Small Molecule Screening at the Duke University Center for Chemical Biology

The Duke University Center for Chemical Biology has available a variety of screening resources. Currently the Center maintains a number of libraries, including the LOPAC library of pharmacologically active compounds and the Prestwick Chemical Library of licensed drugs and biologically active alkaloids. Access to the library is by request of the Director; fees for use include solvents and disposables and Center staff time, billed at $800/day.

The Duke University Center for Chemical Biology works in close collaboration with researchers at the Graduate Medical School in Singapore, a joint initiative of the Duke University School of Medicine and the National University of Singapore. A number of additional libraries and screening resources are now available through this association, and potential users are urged to contact the Director for additional information regarding capabilities and access.

108208 Toone Lab069

In Silico Resources at the Duke University Center for Chemical Biology

The third component of suite of facilities designed to enable research in Chemical Biology is an in silico resource. Modern in silico resources aid research in chemical biology through such strategies as protein and nucleic acid modeling, molecular modeling and visualization, molecular and quantum mechanics, docking library design, and database and diversity analysis. The Center offers a variety of computational tools, including DOCK, autodock, SYBYL, CHARM, Gaussian and Q-Chem, and access to ISIS/Base, Unity, Catalyst, Concord, Corina, Cambridge structural database, and the Brookhaven protein data Bank. The in silico facility operates in Singapore through a joint NUS/Duke venture, and is available to all Duke researchers. Researchers interested in accessing our computational tools should contact the Director or Center staff.

098006 Brady040

Rachel Brady visualizes a protein in the DiVE tank. This fully immersive virtual reality experience gives researchers an unparalleled sense of protein structure.