1. Importance of R-CF3•••O Tetrel Bonding Interactions in Biological Systems.
- Author
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García-LLinás, Xavier, Bauzá, Antonio, Seth, Saikat K., and Frontera, Antonio
- Subjects
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BIOLOGICAL systems , *SYSTEMS theory , *TRIAZINES , *ALKYLATING agents , *ASPARTATES - Abstract
In this article, ab initio calculations have been combined with a search in the Protein Data Bank (PDB) to demonstrate the importance of σ-hole tetrel bonding interactions in biological systems. In particular, we focus our attention on the ability of the -CF3 group to participate in noncovalent interactions as Lewis acids, and we show the importance of this interaction in the inhibition mechanism of a NADP+-dependent isocitrate dehydrogenase (IDH) enzyme that converts isocitrate to α-ketoglutarate. IDH mutations are found in multiple hematologic and solid tumors, inducing premalignant disorders. A potent triazine-based inhibitor of the mutant IDH (enasidenib) presents two-CF3 groups in the structure. One establishes a tetrel bonding interaction with an aspartate residue that contributes to the binding and selectivity of the inhibitor to the active site. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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