Overall schematic of the split luciferin ligation reaction between D- or L-cysteine and hydroxy- or amino-cyanobenzothiazole derivatives (OH-CBT and NH2-CBT) in various biological environments. Adapted with permission from Godinat, A., Park, H. M., Miller, S. C., Cheng, K., Hanahan, D., Sanman, L. E., Bogyo, M., Yu, A., Nikitin, G. N., Stahl, A., Dubikovskaya, E. A. 2013 A Biocompatible In Vivo Ligation Reaction and its Application for Non-Invasive Bioluminescent Imaging of Protease Activity in Living Mice, ACS Chem. Biol. 8, 987–999. Copyright 2014 American Chemical Society.