Transnitrosation of Thiols from Aliphatic N -Nitrosamines: S -Nitrosation and Indirect Generation of Nitric Oxide

S -Nitrosothiols and heme nitrosyl species are nitric oxide (NO)-derived metabolites that provide an endogenous reservoir of NO and also play roles in protein S -nitrosation, that is, transnitrosation of thiols (or thiolates) in proteins, thereby regulating protein functions and signal transduction pathways. Intriguingly, endogenous N -nitrosamines are present in similar abundance to S -nitrosothiols, and though they are thought to play similar physiological roles to S -nitrosothiols, their transnitrosation reactivities and their contribution to biological events are little understood. Herein we report aliphatic N -nitroso derivatives of 7-azabicyclo[2.2.1]heptanes, which do not act as NO donors themselves, but can transnitrosate thiols. On the basis of the calculated activation energies of transnitrosation and the aorta smooth-muscle relaxation activities of these N -nitrosamines, we present a possible scenario of S -transnitrosation from aliphatic N -nitrosamines, leading to indirect generation of NO.