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Mid Atlantic Chapter



February 2001
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The NJ ACS section is pleased to announce the first symposium dedicated to:

 

igh Throughput Biomolecular Screening Using Mass Spectrometric Detection?o:p>

 

3:00 to 8:00 PM on Tuesday, February 13, 2001 at the  
Somerset Marriott Hotel, 110 Davidson Ave. Somerset, NJ

[Directions]  
<http://www.njacs.org/d_sommarr.html>

 

A collaborative effort between the 
Mass Spectrometry Discussion Group (http://www.njacs.org/ms.html) 
and the 

Laboratory Robotics Interest Group
Mid Atlantic Chapter (https://www.lab-robotics.org/Mid_Atlantic/).

   

The symposium will start with an unabridged vendor fair and social period that includes an extensive dinner buffet.  After dinner, lectures will be given by 3 world leaders in biomolecular screening using MS detection.  The lectures are as follows:

 

"Biomolecular Screening Using Ultrafiltration Mass Spectrometry: Assays for Drug Discovery and Development"

Richard B. van Breemen and Dejan Nikolic
Department of Medicinal Chemistry and Pharmacognosy
University of Illinois College of Pharmacy
833 S. Wood Street; Chicago, IL 60612

As a detector for high throughput screening assays, mass spectrometry offers a unique combination of sensitivity, speed and selectivity. In particular, the selectivity of the mass spectrometer facilitates the screening of combinatorial libraries as mixtures instead of discreet compounds thereby increasing the throughput of these assays. Another important aspect of screening mixtures is the ability to screen natural product extracts which have become a neglected source of molecular diversity and lead compounds. Although several mass spectrometry-based assays have been developed for drug discovery and lead optimization, few have been reported for drug development applications such as metabolism screening or toxicity screening. One such method is pulsed ultrafiltration which was invented and developed in our laboratory. Applications of pulsed ultrafiltration mass spectrometry include the screening of natural products and combinatorial libraries for drug discovery, the screening of directed libraries during lead optimization, drug metabolism profiling, toxicity screening of lead compounds for metabolic activation to electrophilic intermediates, and measurement of affinity constants. In summary, the mass spectrometry-based screening technique of pulsed ultrafiltration may be used to facilitate multiple stages of drug discovery and development.



"Using Frontal Affinity Chromatography - Mass Spectrometry (FAC/MS)
for High Throughput Biomolecular Screening"

N. Chan, D. Lewis, M. Middleditch, D. Schriemer
MDS Proteomics, Calgary, Alberta
P. Rosner, M. Kelly
Pfizer Global Research and Development, Groton, CT

The HTS community continues to require technological and assay innovation, however novel approaches require a substantial development and validation period before achieving the status of a reliable screening tool. Numerous assay technologies exist, yet not all are suitable for HTS, primarily due to the high standards of the field (better, faster, cheaper). Once an innovative approach is identified, it needs to pass rigorous tests to ensure reliability, high information content, ability to automate, and scalability.
Scalability is particularly important. While the current trend is to develop smaller, focused compound libraries rather than rely on a massive unfocused library approach, chemistry is not the only pressure on HTS. Progress in target identification, in large part stimulated by the sequencing of the human genome, is beginning to swell the number of assays to be run at any given time.
Chromatography shows promise for alleviating the pressures of a growing workload. MDS Proteomics is currently exploring the application of frontal affinity chromatography (FAC) to several areas of drug discovery, including HTS. This presentation will focus on the fundamentals of the approach and demonstrate their relevance to the needs of the HTS community. Particular emphasis will be placed on the potential for short (and generic) assay development, minimal compound consumption, and direct readout or label-free operation. The technology will be demonstrated with a range of examples, including estrogen receptor, sorbitol dehydrogenase, b-galactosidase and thrombin assays. Innovations in the area of multiplexed assays will be described and illustrated, and the importance of mass spectrometry as a detection scheme will be emphasized. As FAC is a technology under aggressive development, there will be some reflection on the hurdles to be overcome, and opportunities for the future.



"High Performance ESI-FTICR Mass Spectrometry as a High Throughput Affinity Screen to Identify RNA-Binding Ligands"

Steven A. Hofstadler, Jared J. Drader, Richard H. Griffey, Kristin A. Sannes-Lowery, and Sheri Manalili
Ibis Therapeutics, A Division of Isis Pharmaceuticals, Inc.
Carlsbad, CA 92008

Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) is increasingly being used in the drug discovery arena as a tool to characterize macromolecules. In this presentation we describe the development of a parallel high-throughput screening (HTS) strategy to identify small molecules that bind RNA targets using FTICR as an alternative to classical high-throughput screening of combinatorial libraries. The MASS (Multitarget Affinity/Specificity Screening) assay takes advantage of the "intrinsic mass" label of each compound and target RNA by employing high resolution, high precision mass measurements. The ability to analyze complex mixtures allows large mixtures to be screened in the presence of multiple RNA targets simultaneously. The identity of the small molecule(s) which bind, the RNA target to which it binds, the compound-specific binding affinity, and the location of the binding site on the RNA can be determined in one set of rapid experiments. The MASS assay detects noncovalent complexes with dissociation constants of < ~5 mM, with high sensitivity and is presently being employed to screen large compound collections against multiple RNA targets.

 

Vendor Fair 3:00-6:00PM
Dinner 3:30-5:30PM
Lectures: 6:00-8:00PM

 Menu: Extensive Buffet
Cost: FREE!

 

Pre-registration is required.
Please register before February 7, 2001.
Seating is limited; so register early!

[Registration Page]  
<http://www.njacs.org/msregis.html>

Admission is free of charge for this meeting, but pre-registration is required and can be completed on-line at http://www.njacs.org/msregis.html or by E-mailing your name and affiliation to [email protected] during the period from January 15, 2001 to February 6, 2001. Please note that there is a space limit of 400 attendees for this symposium and registration will be cut off when the limit is reached. So, register early to get your spot at this "first of its kind event!"


          


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