Synthesis, characterization, and metabolic stability of porphyrin-peptide conjugates bearing bifunctional signaling sequences
A series of four porphyrin-peptide conjugates bearing one linear bifunctional sequence containing a cell penetrating peptide (CPP) and a nuclear localization signal (NLS) were synthesized and their in vitro biological and stability properties investigated. All conjugates accumulated within human HEp2 cells to a significantly higher extent than their porphyrin - PEG precursor, and the extent of their uptake and cytotoxicity depends on the nature and sequence of the amino acids. Conjugates 2 and 5 bearing a NLS-CPP accumulated the most within cells and were the most phototoxic (IC50 ≈ 7 μM at 1 J/cm2). All conjugates localized preferentially within the cell lysosomes, and in addition, conjugate 2 was also found in the ER. All conjugates were highly stable under nonenzymatic conditions, but their peptide sequences were cleaved to some extent (ca. 50% after 24 h) by proteolytic enzymes, such as cathepsin B, cathepsin D, prolidase, and plasmin. © 2008 American Chemical Society.
Publication Source (Journal or Book title)
Journal of Medicinal Chemistry
Sibrian-Vazquez, M., Jensen, T., & Vicente, M. (2008). Synthesis, characterization, and metabolic stability of porphyrin-peptide conjugates bearing bifunctional signaling sequences. Journal of Medicinal Chemistry, 51 (10), 2915-2923. https://doi.org/10.1021/jm701050j