DC4 crosslinker is a mass spectrometry-cleavable crosslinking reagent (18? in length) that contains two intrinsic positive charges, which allow cross-linked peptides to fragment into their component peptides by collision-induced dissociation or in-source decay. Initial fragmentation events result in cleavage on either side of the positive charges so that cross-linked peptides can be identified as pairs of ions separated by defined masses. Additionally, these two intact peptide fragments can be further fragmented to yield a series of b- and y-ions for peptide identification.