Method to determine protein interaction sites

A crosslinker compound useful for modifying proteins for mass spectral analysis which compound is of Formula (1):

• Reactive group-X1-cleavable site-X2-Reactive group (I)
• wherein each of X1 and X2 is independently a branched or linear spacer moiety comprising a chain of 2-10 atom members selected from the group consisting of carbon, nitrogen, sulfur, and oxygen, wherein each carbon atom is optionally substituted with ═O;
• wherein at least one of X1 and X2 is substituted by an “affinity ligand” that is a moiety having specific affinity for a binding partner;
• wherein each “reactive group” is independently a group that reacts with an amine, hydroxyl, sulfhydryl, or carboxyl group of a protein to form a covalent bond with the protein;
• and
• wherein the “cleavable site” is an MS cleavable linker which comprises a single low energy MS labile bond.