Modulating membrane-bound enzyme activity with chemical stimuli

Membrane-bound enzymes play pivotal roles in various cellular processes, making their activity regulation essential for cellular homeostasis and signaling transduction. Given that dysregulation of membrane-bound enzymes involved in various disease, controlling enzyme activity offers valuable avenues for designing targeted therapies and novel pharmaceutical interventions. This review explores chemical stimuli-responsive strategies for modulating the activity of these enzymes, employing diverse stimuli such as small molecules, proteins, nucleic acids, and bifunctional molecules to either inhibit or enhance their catalytic function. We systematically delineate the mechanisms underlying enzyme activity regulation, including substrate binding site blockade, conformational changes, and local concentration of enzymes and substrates. Furthermore, based on some examples, we elucidate the binding modalities between stimuli and enzymes, along with potential modes of regulation, and discuss their potential medical applications and future prospects. This review underscores the significance of understanding and manipulating enzyme activity on the cell membrane for advancing biomedical research and therapeutic development.