Two Si-Bridge dye isomers with an O 6 -benzylguanine SNAP-tag ligand attached to either face of the dye (78a-b, Figure ) were compared to the commercial dye SNAP-Cell 647-SiR, which has a SNAP-tag ligand attached to the pendant phenyl (Figure ). All three dyes labeled the nucleus in HeLa cells transfected with pSNAPf-H2B (Figure , Figure ). Thus SNAP-tag labeling is tolerant of attachment on either face of the dye via the Si-bridge as well as conventional positioning via the pendant phenyl.