Facilities for Drug Discovery

Facilities for drug discovery in the Department of Chemistry include:

Computer-assisted drug design

Two SGI computers (Indigo 2 Extreme & Octane) printers (HP4M & Tektronic Phaser 2000 color) and modeling software (Sybyl, ISIS, Macromodel, Spartan, MOPAC, & MM3) constitute a molecular modeling facility. Software for combinatorial chemistry library design, diversity metrics analysis, and database searching (including organic reactions databases) is also available. This is located in a newly constructed, specially designed modeling room located on the 2nd floor of the Chemistry Building. The synthetic laboratories are equipped with Ethernet connections and PCs suitable for on-line literature searching, word processing, and data analysis.


Organic synthesis.

Four well-equipped laboratories supporting 4 chemists each are available for synthetic medicinal chemistry. Analytical instrumentation in the Chemistry Department which is used to support the synthetic efforts include: 1) NMR Center [Bruker DRX 400 NMR with 5-mm inverse-detection 1H{X} and 10-mm normal probes; Bruker ARX 300 NMR with a 5-mm 1H/19F/31P/13C probe]; LC-MS Center [MicroMass Platform LCZ LC/MS with HP1100 HPLC/autoinjector and diode array detector]; MALDI-TOF MS Center [PerSeptive Biosystems Voyager Elite DE MALDI/TOF/MS; GC5 and GC45 gas chromatographs]; X-ray Diffraction Center [Enraf-Nonius CAD 4 single crystal diffractometer]; and various optical and infrared spectrometers [AVIV 62DS spectropolarimeter; AVIV 14DS spectrophotometer; Lambda 6 UV/vis; Nicolet; FTIR 44; Perkin Elmer L550 spectrofluorimeter].


Combinatorial Chemistry

Automated robotic combinatorial chemistry workstation: Bohdan Model ARS-100 RAM Robotic synthesizer workstation, including ARS-200 RAM synthesizer heating/cooling/shaking station (-30 - 150 ° C) and ARS -300 Pathogenesis RAM synthesizer. A Gilson 215 robotic liquid handler equipped with a diode array detector and "rapidly-eluting" preparative reverse phase HPLC columns forms a preparative combinatorial chemistry purification workstation. A Savant vacuum centrifuge provides capabilities for concentrating numerous solutions under vacuum at once. Several manual reaction blocks (equipped for heating/stirring/inert gas) and related equipment are also available to assist library preparation.


HPLC Preparative Separations

The HPLC separations facility is across the hall from the synthetic laboratories on the 1st floor. The HPLC laboratory contains two independent computer-controlled, gradient HPLCs using Gilson pumps (25-mL pump heads) and Gilson diode array and variable wavelength UV/vis detectors, and a Gilson combinatorial chemistry preparative HPLC system with diode array detector.

 

Protein Isolation/Purification, Biological Studies, and Biological Spectroscopy

A laboratory (25' x 26') designed for biological separations is across the hall from the synthetic laboratories. The laboratory also has a built-in 4 °C cold room (8' x 10'), 0 °C and -80 °C freezers. The laboratory is equipped with a J-20 Beckmann centrifuge and other routine equipment for biological separations and identifications. The HPLC laboratory contains gradient HPLCs and variable wavelength UV/vis detectors as well as a home-built capillary electrophoresis system used for protein/peptide characterization. Adjoining this lab, a spectroscopy laboratory contains optical instruments for protein structure determination and protein-ligand interaction [ AVIV 62DS spectropolarimeter with thermoelectric device; an AVIV 14DS UV/vis spectrophotometer with a waterbath; Bomem Prota FT-IR, and a laboratory-built UV/vis-fluorescence stopped-flow constructed with a Biologic stopped flow and Oriel optics. Software for protein 2° structure calculation, thermodynamic and kinetic analyses is available.]