Npom‐Protected NONOate Enables Light‐Triggered NO/cGMP Signalling in Primary Vascular Smooth Muscle Cells

Abstract Diazeniumdiolates (NONOates) are a class of nitric‐oxide‐releasing substances widely used in studies of NO/cGMP signalling. Because spatiotemporal control is highly desirable for such purposes, we have synthesised a new Npom‐caged pyrrolidine NONOate. A kinetic analysis together with a Griess assay showed the photodependent release of NO with high quantum yield (UV light). In primary vascular smooth muscle cells (VSMCs), our compound was reliably able to induce fast increases in cGMP, as measured with a genetically encoded FRET‐based cGMP sensor and further validated by the phosphorylation of the downstream target vasodilator‐stimulated phosphoprotein (VASP). Thanks to their facile synthesis, good decaging kinetics and capability to activate cGMP signalling in a fast and efficient manner, Npom‐protected NONOates allow for improved spatiotemporal control of NO/cGMP signalling.