Nitric oxide and thiols: Chemical biology, signalling paradigms and vascular therapeutic potential

Abstract

Nitric oxide (•NO) interactions with biological thiols play crucial, but incompletely determined, roles in vascular signalling and other biological processes. Here, we highlight two recently proposed signalling paradigms: (1) the formation of a vasodilating labile nitrosyl ferrous haem (NO–ferrohaem) facilitated by thiols via thiyl radical generation and (2) polysulfides/persulfides and their interaction with •NO. We also describe the specific (bio)chemical routes in which •NO and thiols react to form S‐nitrosothiols, a broad class of small molecules, and protein post‐translational modifications that can influence protein function through catalytic site or allosteric structural changes. S‐Nitrosothiol formation depends upon cellular conditions, but critically, an appropriate oxidant for either the thiol (yielding a thiyl radical) or •NO (yielding a nitrosonium [NO+]‐donating species) is required. We examine the roles of these collective •NO/thiol species in vascular signalling and their cardiovascular therapeutic potential.