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

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. LINKED ARTICLES This article is part of a themed issue Recent Innovations in Targeting Redox Biology for Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.1/issuetoc