The Applicability of Molecular Descriptors for Designing an Electrospray Ionization Mass Spectrometry Compatible Library for Drug Discovery

Author(s): Jennifer C. Copeland, Levi J. Zehr, Ronald L. Cerny, Robert Powers.

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 15 , Issue 10 , 2012

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Abstract:

Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9% of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ~1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.

Keywords: Chemical library, drug discovery, electrospray ionization, ligand-affinity screens, mass spectrometer, molecular descriptors.

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Article Details

VOLUME: 15
ISSUE: 10
Year: 2012
Page: [806 - 815]
Pages: 10
DOI: 10.2174/138620712803901180
Price: $58

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