Abstract: Weakly basic molecules containing a double bond (in particular vinylpyridines) are able to react and selectively alkylate —SH groups in proteins, thus preventing their re-oxidation to disulphur bridges. Contrary to conventional alkylating agents, such as iodoacetamide, such molecules reach 100% alkylation of all —SH residues, even in complex proteins, without reacting with other functional groups. Their use is particularly effective in proteome analysis and more generally for analysing proteins in which the —SH groups should be blocked. Additionally, the use of vinylpyridines partially or totally deuterated, and thus with a mass difference as compared to non-deuterated vinylpyridines, allows studies of induction/repression of protein synthesis.