Broadly speaking, medicinal chemistry involves applying chemical and molecular approaches applied for the purpose of drug discovery. Given the multidisciplinary nature of medicinal chemistry, the College of Pharmacy conceptualizes medicinal chemistry as consisting of four specialized areas of research:  biochemistry, biophysics, bioinformatics, and organic chemistry.  (Our curriculum for the Medicinal Chemistry PhD program is organized around these four areas.  See Curriculum)

Our faculty's research programs are varied, but many share a common focus on elucidating molecular processes involved in ligand interactions with macromolecules, mechanisms of enzyme catalysis, and signal transduction. 
Research groups use both chemical and biochemical techniques to:

  • Design and synthesize organic molecules as probes
  • Determine steady-state and pre-steady-state kinetics to characterize enzyme-catalyzed reactions and interactions of enzymes and receptors with various ligands
  • Investigate biological structure and function by the generation and characterization of mutant macromolecules using molecular, biological, kinetic, and structural (nuclear magnetic resonance and crystallographic) approaches

Once active compounds have been discovered, major research efforts are dedicated to understanding the molecular basis for the modes of action of new compounds.

Students interested in the biochemical aspects of drug design and action can carry out research on some of the most exciting topics in contemporary biology while obtaining excellent training in a rigorous, chemistry-based program.

Faculty working in the area of Biochemistry include:

  • Carol Fierke (post-translational modifications of proteins, RNA processing, metal metabolism)
  • George Garcia (TB drug discovery, bacterial virulence, and RNA modification )
  • Amanda Garner (chemical biology of mRNA translation, protein-protein interactions, microRNAs)
  • Anna Mapp (mechanistic studies of eukaryotic transcription, protein-protein interactions, kinetics)
  • Brent Martin (post-translational modifications, protein acylation, and oxidation)
  • Hank Mosberg (G protein-coupled receptors, membrane proteins)
  • Nouri Neamati (cell signaling, target identification and validation, preclinical studies)
  • Bruce Palfey (flavin enzymology, pyrimidine redox metabolism)
  • Anna Schwendeman (high density lipoproteins (HDL), atherosclerosis, HDL interactions with cellular proteins, nanomedicine)
  • Emily Scott (drug metabolism and cancer drug design related to human (membrane) cytochrome P450 enzyme structure/function)
  • Peter Scott (non-invasive in vivo imaging of biochemical processes in neurological and oncological disease states using positron emission tomography imaging)
  • David Sherman (natural product biosynthetic enzymes)
  • Matt Soellner (cellular characterization of kinase inhibitors; probing the role of c-Src in cancer cell lines)
  • Duxin Sun (protein-protein interactions, cancer stem cells, biopharmaceutics, pharmacokinetics and drug metabolism, nanotheranostics for drug delivery)
  • Shaomeng Wang (cancer cell biology, basic mechanisms of new anticancer agents and in vivo tumor biology)
  • Ron Woodard (cell wall and aromatic amino acid biosynthesis)

Biophysics is the application of physical techniques to biological systems. These approaches can be experimental or theoretical. Many of the faculty use nuclear magnetic resonance (NMR) data and X-ray crystallography to gain structural insights into protein-ligand interactions. These data are used to explain the effects of mutagenesis and to direct structure-based drug design. Several labs use spectroscopy of small molecules to gain insights into biological systems. These data can elucidate the conformation of ligand molecules, and analyzing NMR data for labeled substrates/products can explain cryptic mechanisms of pharmacologically relevant proteins.

Computational chemistry, statistical mechanics, and molecular modeling can clarify complex biological data. These techniques are central to computer-aided drug discovery and protein folding prediction. Models of protein-ligand interactions can unlock the biophysical patterns that govern molecular recognition. Key issues include: ligand docking, scoring functions, protein flexibility, protein folding, and the predictive power of the resulting models.

Faculty working in the area of Biophysics area include:

  • Charles L. Brooks III (protein simulations, structure-based drug discovery)
  • Heather Carlson (protein simulations, structure-based drug discovery)
  • Brent Martin (mass spectrometry, proteomics)
  • Hank Mosberg (G-protein--coupled receptors, membrane proteins)
  • Nouri Neamati (structure and ligand-based drug design, assay development)
  • Bruce Palfey (kinetics, thermodynamics, and single-molecule spectroscopy)
  • Anna Schwendeman (peptide-phospholipid interactions, lipid nano-rafts for membrane protein structure elucidation)
  • Emily Scott (drug metabolism and cancer drug design related to human (membrane) cytochrome P450 enzyme structure/function)  
  • John Tesmer (molecular basis of GPCR-mediated signal transduction, X-ray crystallography)
  • Janet Smith (molecular mechanisms of proteins, X-ray crystallography)
  • Shaomeng Wang (protein simulations, protein-ligand interactions, binding free-energy predictions, and structure-based drug discovery)

Computers run much of our laboratory equipment, store huge databases of genomic and chemical information, and model drugs interacting with biological receptors at the molecular level.  Experts in this field work with computers to develop complex statistical or physical models and validate them against large sets of experimental results.  Many faculty develop mathematical models to analyze physical and biological assay data, and to gain insights into drug mechanisms of action, protein-ligand interactions and ADME-Tox properties.

The large size of the datasets and the programming-intensive techniques for data mining are what set bioinformatics apart from the more theoretical biophysical studies. Bioinformatic studies at the College of Pharmacy focus heavily on research insights, database development, and new mining techniques. The College does not offer masters-level studies for academic librarians.

Faculty working in the area of Bioinformatics area include:

  • Charles L. Brooks III (protein simulations, structure-based drug discovery)
  • Heather Carlson (protein-ligand databases, mining patterns of molecular recognition)
  • Carol Fierke (high throughput screening)
  • Nouri Neamati (high throughput screening, chemoinformatics, proteomics and genomics analysis, pathway analysis, target identification)
  • David Sherman (high throughput screening, genomic analysis)
  • Shaomeng Wang (computational and informatics methods and tools for drug design and discovery)

Faculty investigate a wide variety of challenging problems in synthetic organic chemistry. A common focus is the use of modern synthetic methods to prepare complex organic molecules for use in the study of a number of important biological problems. Students receive excellent training in organic synthesis while learning the biochemical aspects of drug design and evaluation.

For example, the design, synthesis, and biological evaluation of artificial activators of gene expression are an ongoing efforts, as is the stereoselective synthesis of beta-amino acids for a variety of biochemical and synthetic applications. The discovery/development of new transition metal-catalyzed reactions and new synthetic methods for use in the synthesis of complex molecules is also an active area of research. Modern methods of heterocyclic synthesis are being used to make complex drug-like molecules for inhibiting novel targets in infectious diseases and cancer. A more recent effort involves "hit to lead" campaigns, in which a small molecule inhibitor derived from screening against a biological target is optimized synthetically into a drug-like molecule by developing structure-activity relationships (SAR). The design and synthesis of radiopharmaceuticals is an area of research that is rarely found in medicinal chemistry departments.

Faculty working in the area of Organic Chemistry include:

  • Amanda Garner (design and synthesis of chemical probes targeting protein-protein interactions and RNAs, small molecule library synthesis, new synthetic methods)
  • Scott Larsen (optimization of small molecule screening leads for proof-of-concept studies in vivo, target identification)
  • Anna Mapp (organic chemistry, chemical biology, new synthetic methods)
  • Brent Martin (fluorescent probes, bio-organic chemistry, medicinal chemistry)
  • John Montgomery (organic chemistry, organometallic chemistry, complex molecule synthesis)
  • Hank Mosberg (design and synthesis of peptide and peptidomimetic ligands)
  • Nouri Neamati (design and synthesis of novel small-molecule drugs targeting mitochondria, ER stress proteins, transcription factors, receptors, and GPCRs)
  • Anna Schwendeman (design of lipoprotein mimetic peptides)
  • Peter Scott (design and synthesis of novel small molecules that can be radiolabeled with fluorine-18 or carbon-11 to generate radiopharmaceuticals for positron emission tomography imaging; solid-phase organic synthesis)
  • David Sherman (natural products and intermediates as substrates for biosynthetic enzymes)
  • Hollis Showalter (anti-infectives and anti-cancer drug discovery; hit-to-lead SAR development; heterocyclic synthesis)
  • Matt Soellner (small-molecule inhibitor design and synthesis; combinatorial chemistry and chemical biology)
  • Shaomeng Wang (design and synthesis of novel small-molecule ligands to target protein-protein interactions, apoptosis regulators and G-protein--coupled receptors, chemical biology)
Biochemistry

Our faculty's research programs are varied, but many share a common focus on elucidating molecular processes involved in ligand interactions with macromolecules, mechanisms of enzyme catalysis, and signal transduction. 
Research groups use both chemical and biochemical techniques to:

  • Design and synthesize organic molecules as probes
  • Determine steady-state and pre-steady-state kinetics to characterize enzyme-catalyzed reactions and interactions of enzymes and receptors with various ligands
  • Investigate biological structure and function by the generation and characterization of mutant macromolecules using molecular, biological, kinetic, and structural (nuclear magnetic resonance and crystallographic) approaches

Once active compounds have been discovered, major research efforts are dedicated to understanding the molecular basis for the modes of action of new compounds.

Students interested in the biochemical aspects of drug design and action can carry out research on some of the most exciting topics in contemporary biology while obtaining excellent training in a rigorous, chemistry-based program.

Faculty working in the area of Biochemistry include:

  • Carol Fierke (post-translational modifications of proteins, RNA processing, metal metabolism)
  • George Garcia (TB drug discovery, bacterial virulence, and RNA modification )
  • Amanda Garner (chemical biology of mRNA translation, protein-protein interactions, microRNAs)
  • Anna Mapp (mechanistic studies of eukaryotic transcription, protein-protein interactions, kinetics)
  • Brent Martin (post-translational modifications, protein acylation, and oxidation)
  • Hank Mosberg (G protein-coupled receptors, membrane proteins)
  • Nouri Neamati (cell signaling, target identification and validation, preclinical studies)
  • Bruce Palfey (flavin enzymology, pyrimidine redox metabolism)
  • Anna Schwendeman (high density lipoproteins (HDL), atherosclerosis, HDL interactions with cellular proteins, nanomedicine)
  • Emily Scott (drug metabolism and cancer drug design related to human (membrane) cytochrome P450 enzyme structure/function)
  • Peter Scott (non-invasive in vivo imaging of biochemical processes in neurological and oncological disease states using positron emission tomography imaging)
  • David Sherman (natural product biosynthetic enzymes)
  • Matt Soellner (cellular characterization of kinase inhibitors; probing the role of c-Src in cancer cell lines)
  • Duxin Sun (protein-protein interactions, cancer stem cells, biopharmaceutics, pharmacokinetics and drug metabolism, nanotheranostics for drug delivery)
  • Shaomeng Wang (cancer cell biology, basic mechanisms of new anticancer agents and in vivo tumor biology)
  • Ron Woodard (cell wall and aromatic amino acid biosynthesis)
Biophysics

Biophysics is the application of physical techniques to biological systems. These approaches can be experimental or theoretical. Many of the faculty use nuclear magnetic resonance (NMR) data and X-ray crystallography to gain structural insights into protein-ligand interactions. These data are used to explain the effects of mutagenesis and to direct structure-based drug design. Several labs use spectroscopy of small molecules to gain insights into biological systems. These data can elucidate the conformation of ligand molecules, and analyzing NMR data for labeled substrates/products can explain cryptic mechanisms of pharmacologically relevant proteins.

Computational chemistry, statistical mechanics, and molecular modeling can clarify complex biological data. These techniques are central to computer-aided drug discovery and protein folding prediction. Models of protein-ligand interactions can unlock the biophysical patterns that govern molecular recognition. Key issues include: ligand docking, scoring functions, protein flexibility, protein folding, and the predictive power of the resulting models.

Faculty working in the area of Biophysics area include:

  • Charles L. Brooks III (protein simulations, structure-based drug discovery)
  • Heather Carlson (protein simulations, structure-based drug discovery)
  • Brent Martin (mass spectrometry, proteomics)
  • Hank Mosberg (G-protein--coupled receptors, membrane proteins)
  • Nouri Neamati (structure and ligand-based drug design, assay development)
  • Bruce Palfey (kinetics, thermodynamics, and single-molecule spectroscopy)
  • Anna Schwendeman (peptide-phospholipid interactions, lipid nano-rafts for membrane protein structure elucidation)
  • Emily Scott (drug metabolism and cancer drug design related to human (membrane) cytochrome P450 enzyme structure/function)  
  • John Tesmer (molecular basis of GPCR-mediated signal transduction, X-ray crystallography)
  • Janet Smith (molecular mechanisms of proteins, X-ray crystallography)
  • Shaomeng Wang (protein simulations, protein-ligand interactions, binding free-energy predictions, and structure-based drug discovery)
Bioinformatics

Computers run much of our laboratory equipment, store huge databases of genomic and chemical information, and model drugs interacting with biological receptors at the molecular level.  Experts in this field work with computers to develop complex statistical or physical models and validate them against large sets of experimental results.  Many faculty develop mathematical models to analyze physical and biological assay data, and to gain insights into drug mechanisms of action, protein-ligand interactions and ADME-Tox properties.

The large size of the datasets and the programming-intensive techniques for data mining are what set bioinformatics apart from the more theoretical biophysical studies. Bioinformatic studies at the College of Pharmacy focus heavily on research insights, database development, and new mining techniques. The College does not offer masters-level studies for academic librarians.

Faculty working in the area of Bioinformatics area include:

  • Charles L. Brooks III (protein simulations, structure-based drug discovery)
  • Heather Carlson (protein-ligand databases, mining patterns of molecular recognition)
  • Carol Fierke (high throughput screening)
  • Nouri Neamati (high throughput screening, chemoinformatics, proteomics and genomics analysis, pathway analysis, target identification)
  • David Sherman (high throughput screening, genomic analysis)
  • Shaomeng Wang (computational and informatics methods and tools for drug design and discovery)
Organic Chemistry

Faculty investigate a wide variety of challenging problems in synthetic organic chemistry. A common focus is the use of modern synthetic methods to prepare complex organic molecules for use in the study of a number of important biological problems. Students receive excellent training in organic synthesis while learning the biochemical aspects of drug design and evaluation.

For example, the design, synthesis, and biological evaluation of artificial activators of gene expression are an ongoing efforts, as is the stereoselective synthesis of beta-amino acids for a variety of biochemical and synthetic applications. The discovery/development of new transition metal-catalyzed reactions and new synthetic methods for use in the synthesis of complex molecules is also an active area of research. Modern methods of heterocyclic synthesis are being used to make complex drug-like molecules for inhibiting novel targets in infectious diseases and cancer. A more recent effort involves "hit to lead" campaigns, in which a small molecule inhibitor derived from screening against a biological target is optimized synthetically into a drug-like molecule by developing structure-activity relationships (SAR). The design and synthesis of radiopharmaceuticals is an area of research that is rarely found in medicinal chemistry departments.

Faculty working in the area of Organic Chemistry include:

  • Amanda Garner (design and synthesis of chemical probes targeting protein-protein interactions and RNAs, small molecule library synthesis, new synthetic methods)
  • Scott Larsen (optimization of small molecule screening leads for proof-of-concept studies in vivo, target identification)
  • Anna Mapp (organic chemistry, chemical biology, new synthetic methods)
  • Brent Martin (fluorescent probes, bio-organic chemistry, medicinal chemistry)
  • John Montgomery (organic chemistry, organometallic chemistry, complex molecule synthesis)
  • Hank Mosberg (design and synthesis of peptide and peptidomimetic ligands)
  • Nouri Neamati (design and synthesis of novel small-molecule drugs targeting mitochondria, ER stress proteins, transcription factors, receptors, and GPCRs)
  • Anna Schwendeman (design of lipoprotein mimetic peptides)
  • Peter Scott (design and synthesis of novel small molecules that can be radiolabeled with fluorine-18 or carbon-11 to generate radiopharmaceuticals for positron emission tomography imaging; solid-phase organic synthesis)
  • David Sherman (natural products and intermediates as substrates for biosynthetic enzymes)
  • Hollis Showalter (anti-infectives and anti-cancer drug discovery; hit-to-lead SAR development; heterocyclic synthesis)
  • Matt Soellner (small-molecule inhibitor design and synthesis; combinatorial chemistry and chemical biology)
  • Shaomeng Wang (design and synthesis of novel small-molecule ligands to target protein-protein interactions, apoptosis regulators and G-protein--coupled receptors, chemical biology)

Listing Row

Wednesday, August 28, 2013
Wednesday, August 28, 2013