The applicability of molecular descriptors for designing an electrospray ionization mass spectrometry compatible library for drug discovery.
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.
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA.
Jennifer C
JC
Copeland
Levi J
LJ
Zehr
Ronald L
RL
Cerny
Robert
R
Powers
D020650:Combinatorial Chemistry Techniques; D055808:Drug Discovery; D054852:Small Molecule Libraries / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D054852:Small Molecule Libraries