March 2011 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
PLEASE NOTE: We will meet in Mendel 154.
- Topic: "The Evolution of Mass Spectral Support for Drug Discovery and Recent Applications"
- Speaker: John A. Masucci, Johnson and Johnson Pharmaceutical
- Date: Monday, March 14, 2011. 6:30 PM
- Time: Social Hour: 6:30 PM.
Talk: 7:30 PM.
Please RSVP to Karen Wendling WendlingK@chc.edu by Thursday March 10th.
- Place: Department of Chemistry, Villanova University (Room 154, Mendel Hall)
During the 1970's and early 80's mass spectrometry was utilized in drug discovery almost exclusively for support of medicinal chemistry in which GC/MS and solids inlet probe/MS were primary tools for analysis of synthetic products. With the development of LC-MS following the introductions of thermospray, particle beam interface, electrospray and APCI, and the introduction of MALDI-TOF, mass spectrometry has also become a tool for support of early determination of in-vitro and in-vivo ADME properties of drugs and protein and peptide analysis. More recently LC-MS has also been utilized for determination of compound efficacies via quantitation of enzyme products or substrates called target engagement markers and is now deeply entrenched in direct support of in-vitro and in-vivo pharmacology.
Two recent examples of the use of MS technology in our laboratory will be presented. The first involves the use of iTRAQ peptide labeling for quantitation of MACS2 variants from human mitochondrial extract. MACS2 (medium chain acyl CoA synthetase) is an enzyme involved in ligation of medium chain fatty acids with coenzyme A and is a putative target for metabolic disease. There are three forms of MACS2; two forms of type 2A which differ by a single aa substitution and one form of type 2B which differs by 14 aa substitutions over a 64kDa, 577 aa protein. To quantitate these three forms from human tissue, we utilized unique signature peptides of each form and analyzed using MRM analysis of iTRAQ labeled peptides.
The second example involves the use of the Biocius RapidFire MS inlet system for in-vitro ADME support. The RapidFire device allows MS analysis of samples directly from 96 or 384 well microtiter plates every 10 seconds. The unit was originally designed for high throughput screening of compounds for those assays that require MS detection of enzymatic products. It has also been shown useful for in-vitro and in-vivo ADME support. Some recent data from our research efforts demonstrating its utility in these areas will be presented.
- Bio: Dr. John Masucci is currently a Research Fellow with Johnson and Johnson Pharmaceutical in Spring House, PA where he began his career in 1983 as a Research Associate. During this time John has specialized in the use of mass spectrometry to support drug discovery activities including medicinal chemistry, in-vitro and in-vivo ADME, protein analysis and his current area of focus in analysis of target engagement biomarkers as demonstration of drug efficacy. Major accomplishments during this time include the implementation of open access GC/MS and LC/MS support and introduction of early, rapid pharmacokinetic support in drug discovery. He earned a B.S. in Chemistry from Drexel University and completed his M.S. and Ph.D. at Villanova University as a part-time student while employed with J&J. His thesis work, under the co-direction of Professor Joe Foley (currently at Drexel U.) and Dr. Gary Caldwell (J&J), involved the development of a novel, microdialysis membrane interface for capillary electrophoresis-mass spectrometry. John began his interest in mass spectrometry while employed as a Drexel co-op student at the USDA Eastern Regional Research Laboratories. John has authored or coauthored more than 50 papers and two book chapters.
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