Updated project metadata. To enable global PPI mapping, we have explored an alternative cysteine labeling chemistry, and thus designed and synthesized a sulfoxide-containing MS-cleavable haloacetamide-based cross-linker, DiBromoAcetamide SulfOxide (DBrASO). In combination with a newly developed SEC-HpHt fractionation method, we have successfully applied DBrASO for cross-linking of HEK293 cell lysates and demonstrated its capability to complement lysine-reactive reagents in order to expand PPI coverage at systems-level.