A four amino-acid sequence (FCPF, termed as “π-clamp”) has been introduced for the site-specific cysteine labeling of peptides and proteins in aqueous media. This short sequence undergoes selective and rapid cysteine arylation with perfluorobiphenyl (PFBP) derivatives without the need of catalysts. Given the rich photophysical and photochemical properties of rhenium(I) polypyridine complexes such as their long-lived triplet emission and efficient singlet oxygen generation, these complexes have been widely exploited for biological applications. Herein, we report rhenium(I) PFBP complexes that specifically labeled the cysteine residue of the π-clamp sequence. The complexes were reacted with π-clamp-modified peptides to afford novel conjugates that selectively stained the lysosomes and mitochondria of KYSE-510 cells. The photocytotoxic activity of the conjugates was also investigated. Furthermore, a phosphorogenic substrate for caspase-3/7 was developed to monitor the activity of these enzymes in live cells.

We thank the funding support from the Hong Kong Research Grants Council (Project No. CityU 11302820, CityU 11300019, CityU 11300318, and T42-103/16-N).

Reference

Leung, P. K.-K.; Lee, L. C.-C.; Ip, T. K.-Y.; Liu, H.-W.; Yiu, S.-M.; Lee, N. P.; Lo, K. K.-W. Chem. Commun. 2021, 57, 11256 – 11259.