Peptide-mediated cell transport of water soluble porphyrin conjugates.
Five new porphyrin-peptide conjugates bearing a nuclear localizing sequence SV40 or a fusogenic peptide (HIV-1Tat 40-60 or octa-arginine) linked by low molecular weight poly(ethylene glycol) have been synthesized. In vitro studies using human HEp2 cells show that the cellular uptake of the conjugates depends significantly on the nature and sequence of amino acids in the peptide and on the nature of the substituents on the porphyrin macrocycle. The fusogenic peptide sequences HIV-1Tat 40-60 and octa-arginine were the most effective in delivering the conjugates to the cells. The subcellular distribution of the conjugates was found to be dependent on the nature of substituents on the porphyrin macrocycle. The conjugates bearing a hydrophobic porphyrin localized preferentially in the endoplasmic reticulum and were significantly more phototoxic to HEp2 cells than the carboxylic acid functionalized porphyrin conjugates, which localized mainly in the lysosomes.
Sibrian-Vazquez
Martha
M
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Jensen
Timothy J
TJ
Hammer
Robert P
RP
Vicente
M Graça H
MG
D001120:Arginine / Q000737:chemistry; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003624:Darkness; D004337:Drug Carriers; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015696:Gene Products, tat / Q000737:chemistry; D006801:Humans; D008027:Light; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
D004337:Drug Carriers; D015696:Gene Products, tat; D009842:Oligopeptides; D010446:Peptide Fragments; D017319:Photosensitizing Agents; D011166:Porphyrins; C402304:SV40 nuclear localization peptide; D054322:tat Gene Products, Human Immunodeficiency Virus; C422951:tat peptide (48-60), Human immunodeficiency virus 1; D001120:Arginine