Enhanced cellular uptake with a cobaltacarborane-porphyrin-HIV-1 Tat 48-60 conjugate.
A series of four porphyrin-cobaltacarborane conjugates have been synthesized, containing three or four cobaltabisdicarbollide anions linked by O(CH(2)CH(2)O)(2) groups to the porphyrin macrocycle and one of them containing a HIV-1 Tat 48-60 peptide sequence linked via a low molecular weight poly(ethylene glycol) (PEG) spacer. The cellular uptake, cytotoxicity, and preferential sites of intracellular localization of the conjugates were evaluated in human HEp2 cells. All conjugates are nontoxic in the dark at the concentrations studied. Upon exposure to low light dose (1 J cm(-)(2)) only the porphyrin-cobaltacarborane-HIV-1 Tat 48-60 conjugate showed 30% inhibition of cell proliferation at a concentration of 10 microM. The cellular uptake was dependent on the number of carborane cages and was significantly enhanced by the presence of the cell penetrating peptide sequence HIV-1 Tat 48-60. All conjugates preferentially localized in the cell lysosomes.
Sibrian-Vazquez
Martha
M
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Hao
Erhong
E
Jensen
Timothy J
TJ
Vicente
M Graça H
MG
D002460:Cell Line; D015696:Gene Products, tat / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet; D054322:tat Gene Products, Human Immunodeficiency Virus; D000098851:Carboranes
D015696:Gene Products, tat; D010446:Peptide Fragments; D011166:Porphyrins; D054322:tat Gene Products, Human Immunodeficiency Virus; C515487:cobaltacarborane; D000098851:Carboranes; C422951:tat peptide (48-60), Human immunodeficiency virus 1