Synthesis, phototoxicity and metabolic stability of porphyrins conjugated to bifunctional peptide sequences

BIOT 216

Maria Graca H. Vicente, vicente@lsu.edu and Martha Sibrian-Vazquez, sibrian@lsu.edu. Department of Chemistry, Louisiana State University, 433 Choppin Hall, S. Tower Dr, Baton Rouge, LA 70803
We have been investigating the conjugation of photosensitizing agents for the photodynamic therapy of cancer to certain peptide sequences in order to improve their specific delivery to targeted cells and organelles. The peptide signaling sequences investigated include cell penetrating peptides (CPP) and nuclear or mitochondria localization sequences (NLS, MLS). Our studies show that conjugates of photosensitizers to CPP or NLS/MLS peptides have enhanced photoactivity in vitro compared with the non-conjugated photosensitizers. The biological efficacy of the conjugates depends on the nature and sequence of the amino acids, the porphyrin peripheral substituents, the linker, their conformation(s) in aqueous solutions, amphiphilic character and metabolic stability. We will report our most recent results on the synthesis and properties of photosensitizer conjugates to one or more linear bifunctional peptide(s) composed of CPP and NLS or MLS peptide chains. Their uptake, subcellular localization, phototoxicity and enzymatic stability were investigated in human carcinoma HEp2 cells.