Fmoc-Phe-Aca: Fluorescent Internalization Reporter for Cell Penetrating Peptides (CPPs)

Fmoc-Phe-Aca: Fluorescent Internalization Reporter for Cell Penetrating Peptides (CPPs)

Published on 27.01.2016

The Fmoc-L-Phe-Aca pseudo-dipeptide is a useful reporter group for the successful internalization of CPPs. Phe quenches the fluorescence of Aca. Internalization of the peptide containing Phe-Aca leads to proteolytic cleavage of the Phe-Aca bond and thus to fluorescence.

Fmoc-Phe-Aca: Fluorescent Internalization Reporter for Cell Penetrating Peptides (CPPs)

The unnatural amino acid Aca (7-amino-coumarin-4-acetic acid) is a coumarin derivative and thus exhibits fluorescence. When incorporated into a peptide C-terminally of phenylalanine, Aca is a useful reporter group for the successful internalization of CPPs. The phenyl moiety of Phe quenches the fluorescence of Aca. Internalization of the CPP containing Phe-Aca leads to proteolytic cleavage of the Phe-Aca bond and thus to fluorescence.

However, the peptide bond formation between Phe and Aca is considered to be a difficult coupling and often leads to low coupling yields. For your convenience, Iris Biotech offers Fmoc Phe-Aca as building block suitable for SPPS. This pseudodipeptide can be coupled to the resin of your choice and subsequently elongated to prepare your target cell penetrating peptides.

Loading of a solid support, subsequent elongation to CPPs and function as a reporter group for successful CPP internalization

References:

  • Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries; J. L. Harris, B. J. Backes, F. Leonetti, S. Mahrus, J. A. Ellman and C. S. Craik; Proceedings of the National Academy of Sciences 2000; 97: 7754-7759. doi:10.1073/pnas.140132697
  • Expedient Solid-Phase Synthesis of Fluorogenic Protease Substrates Using the 7-Amino-4-carbamoylmethylcoumarin (ACC) Fluorophore; D. J. Maly, F. Leonetti, B. J. Backes, D. S. Dauber, J. L. Harris, C. S. Craik and J. A. Ellman; The Journal of Organic Chemistry 2002; 67: 910-915. doi:10.1021/jo016140o