Complementary Benzophenone Cross-Linking/Mass Spectrometry Photochemistry

Use
of a heterobifunctional photoactivatable cross-linker, sulfo-SDA
(diazirine), has yielded high-density data that facilitated structure
modeling of individual proteins. We expand the photoactivatable chemistry
toolbox here with a second reagent, sulfo-SBP (benzophenone). This
further increases the density of photo-cross-linking to a factor of
20× over conventional cross-linking. Importantly, the two different
photoactivatable groups display orthogonal directionality, enabling
access to different protein regions, unreachable with a single cross-linker.