Faculty within the Department of Chemistry have well-established research programs in drug discovery. Presently departmental laboratories are devoted toward drug design, synthesis, and characterization. Additionally there is also a strong effort placed in protein receptor characterization and protein receptor-drug interactions. The significant research holding of these laboratories are listed in more detail below.
Ongoing research projects include retinoids as chemopreventive and chemotherapeutic agents, inhibitors of influenza neuraminidase as orally active flu drugs, inhibitors of NAD synthetase as broad spectrum antibiotics, and ligands for the voltage-gated sodium channel as therapies for stroke. The Department of Chemistry at UAB has placed a strong commitment to expand its research effort in drug development.
Special opportunities exist for new faculty with expertise that would enhance these efforts. This includes:
- Organic/Medicinal Chemists who are interested in synthetic chemistry, especially combinatorial chemistry and/or multi-step small molecule synthesis
- Bioanalytical Chemists who are interested in developing new methods for characterization of combinatorial libraries and/or methods for screening libraries
- Biophysical Chemists interested in using spectroscopic/computational approaches to understanding key drug-receptor interactions
UAB is a leading academic health center and research institute with over $470 million in grants and contracts. The majority of this funding is used to support clinically-based research and basic research in the medical area. The research environment is uniquely built upon the Research Center concept, where faculties from different departments gather to form strong research cores.
Especially prominent at UAB are the Comprehensive Cancer Center, AIDS Research Center, Cystic Fibrosis Research Center, Vision Sciences Research Center, and Center for Macromolecular Crystallography (which has a strong program in structure-based drug design). These Centers traditionally allow new faculty to compete for starter grants, foster new research efforts, and provide opportunities to establish collaborations with more senior faculty.
The Birmingham area also offers opportunities for interactions/collaborations:
- BioCryst Pharmaceuticals, Inc. utilizes protein crystallography and structure-based drug design to develop new drugs. Several of their compounds are in clinical trials, and they interact extensively with UAB faculty.
- Southern Research Institute, a nonprofit research organization, has developed several anti-cancer agents that have entered clinical trials. They are now starting a new for-profit pharmaceutical company in Birmingham that will emphasize combinatorial chemistry and high-throughput screening, coupled with structure-based drug design, to develop new clinical drug candidates.
Equipment and Facilities
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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.
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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].
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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.
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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.
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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.]