DSSBU: An MS-Cleavable Analogue of the BS3 Cross-Linker

In this study, we introduce a new MS-cleavable cross-linker called disulfodisuccinimidyl dibutyric urea (DSSBU), which we developed in-house. DSSBU contains an N-hydroxysulfosuccinimide (sulfo-NHS) reactive group that primarily modifies lysine residues. It therefore serves as a water-soluble counterpart to the commercially available and widely used disuccinimidyl dibutyric urea (DSBU). To investigate the applicability of DSSBU, we compared the efficacy of four similar cross-linkers—bis[sulfosuccinimidyl] suberate (BS3), disuccinimidyl suberate (DSS), DSBU, and DSSBU—when used with the common model protein, bovine serum albumin (BSA).