Moulder Center Capabilities
Our capabilities include:
Medicinal Chemistry
We synthesize, purify, and study organic molecules. Our chemistry laboratories are designed to handle milligram-killigram scale small molecule synthesis. We have parallel synthesis platforms for the preparation of either diversity driven or focused libraries of tens-thousands of compounds on 10–100 mg scale. We handle large scale synthesis to meet the needs of PK studies, in vivo animal studies, and CGMP production.
Biotherapeutics
The biotherapeutics laboratory has state-of-the-art discovery capabilities for work on protein-based drugs. Drawing on over 30 years of academic and industrial experience in prokaryotic, eukaryotic and viral molecular genetics, heterologous protein expression, and therapeutic antibody discovery and engineering, we utilize phage display technology as our primary protein discovery platform. We are the only academic group in the world with access to the “Ylanthia” Fab display phage library, a powerful industrial-quality human antibody discovery platform.
Proteomics
We handle expression profiles, protein identification, posttranslational modification, characterization, isolation of individual cells from tissues, protein and peptide separations, capillary electrophoresis, and multidimensional protein identification (MudPIT). Our facility is capable of generating high fidelity data for biomarker discovery, drug targets and studies on the pathogenesis of disease. Our proteomics laboratory and faculty provide accessible proteomics capability for biological and biomedical research.
Solid Phase Peptide Synthesis
We conduct peptide synthesis and purification, as well as identification and characterization of proteins from recombinant or biofluidic sources, using state-of-the-art Solid Phase Peptide Synthesis (SPPS ) equipment, including the CEM Liberty 1 Microwave Peptide Synthesizer.
In Vitro Assay Development and Screening
Our high throughput screening capabilities are built around two Janus Automated Workstations (Varipsan and MDT) capable of supporting 96-well or 384-well platforms. The system supports multiple in vitro and cellular assay paradigms for the study of enzymes, receptors, ion channels and transporter proteins.
To support high throughput screening, we have a 40,000 member small molecule diversity-based screening library that includes linear and cyclic peptides and the Prestwick 1,200 member library of FDA approved drugs. We have a license for the Dotmatics Informatics Platform (Dotmatics, Ltd) to support the chemical database, high throughput screening data management, structure activity relationship (SAR) analysis, and data visualization.
The following supports this work:
- In vivo assay development and screening
- micro dissection
- behavioral assessment
- conditioned place preference
- analgesia and tolerance
- Ex vivo Assay Development and Screening
- radio ligand
- homogenate binding
- autoradiography
- rubidium efflux
- receptor profiling
- drug affinities
- subunit composition
- quantification and distribution
- protein and neuron characterization
- western blotting
- immunohistochemistry
- HPLC
- synaptosomal preparations
- Other specialized capabilities
- pharmacogenomic analysis of SNPs
- copy number variations
- cell-based assays
- cytotoxicity
- apoptosis
- caspase activation
- cell viability
- in-vitro metabolism
- pre-clinical PK
In Vitro Absorption, Distribution, Metabolism and Excretion (ADME) and Pharmacokinetics (PK)
We are equipped to provide a wide range of in vitro ADME/PK studies, drug metabolism studies and in vivo PK studies in support of drug discovery programs.
The following supports this work:
- In vitro assays
- microsomal stability – human and preclinical species
- hepatocyte stability to determine direct conjugation or metabolism by aldehyde oxidase
- unbound fraction assays for equilibrium dialysis and LC/MSMS analysis and interpretation
- CYP inhibition assays for CYP3A4, CYP2D6 and CYP2C9
- permeability assays for CACO-2 and MDCK for correlation with absorption and BBB
- metabolite ID for issue preparations, expressed enzymes and LC/MSMS identification
- In vivo assays
- preclinical pharmacokinetics for mouse and rat studies (IV and oral) to determine
- volume of distribution
- clearance
- half-life
- bioavailability
- CNS penetration for mouse and rat with SC, IP, or IV administration