Mechanism-Based Inactivation of Human Ornithine Aminotransferase by Ethynyl- and Nitrile-Substituted Cyclopentene Analogues of γ-Aminobutyric Acids.
The rational design, synthesis, and mechanistic investigation of cyclopentene-based γ-aminobutyric acid analogues bearing alkyne or nitrile warheads as potent hOAT inactivators are reported, expanding the mechanistic repertoire of PLP-dependent enzyme inactivation and providing a generalizable framework for designing highly selective mechanism-based inactivators.