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Phospholipase A (PLA) enzymes play a major role in many diseases including the inflammatory cascade and specific potent small molecule inhibitors could be useful in studying their physiological role as well as for the development of drugs. In order to discover novel small molecule inhibitor platforms for members of the PLA superfamily of enzymes, we have applied computational approaches to determine the binding mode of potent inhibitors specific for particular PLAs to the screening of chemical libraries. This has including the U.S. National Institutes of Health (NIH) National Cancer Institute (NCI) Diversity Set V and the ChemBridge commercial compound libraries. We have then subjected identified inhibitor structures to recently developed lipidomics based screening assays to determine the X(50) and specificity of the identified compounds for specific PLAs. Herein we review this approach and report the identity of initial hits for both the Group IVA cytosolic PLA and the Group VIA calcium-independent PLA that are worthy of further structural modification to develop novel platforms for inhibitor development.
This article was published in the following journal.
Name: Advances in biological regulation
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Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.
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A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior.
Ability to identify an individual and interpret their feelings and emotions based on their facial expressions.
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