A protein transduction domain located at the NH2-terminus of human translationally controlled tumor protein for delivery of active molecules to cells.
Protein transduction domains (PTDs) are small peptides, able to penetrate biological membranes and deliver various types of cargo both in vitro and in vivo. Because use of PTDs originating from viral origins resulted in undesired effects, PTDs originating from non-viral origins are needed. Here, we report that a 10-amino acid peptide (MIIYRDLISH) derived from the NH(2)-terminus of human translationally controlled tumor protein (TCTP) functions as a PTD. This peptide was internalized through lipid raft-dependent endocytosis and partial macropinocytosis, and did not enter lysosome and nucleus. Beta-galactosidase fused to TCTP-PTD, when injected into mice, was efficiently delivered to liver, kidney, spleen, heart, and lungs of the animals. Preincubation of TCTP-PTD with adenovirus increased adenoviral mediated-gene expression in cells and also improved immune response to intranasally administered adenovirus expressing the triple repeat of G glycoprotein of respiratory syncytial virus (RSV), rAd/3×G. These findings suggest that TCTP-PTD might overcome the limitations of polycation-mediated transduction and serve as an efficient vehicle for drug delivery.
Kim
Moonhee
M
College of Pharmacy, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Republic of Korea.
Kim
Miyoung
M
Kim
Hyo Young
HY
Kim
Sol
S
Jung
Jaehoon
J
Maeng
Jeehye
J
Chang
Jun
J
Lee
Kyunglim
K
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D015870:Gene Expression; D015696:Gene Products, tat / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014161:Transduction, Genetic; D000090324:Tumor Protein, Translationally-Controlled 1; D001616:beta-Galactosidase / Q000378:metabolism
D014408:Biomarkers, Tumor; D015696:Gene Products, tat; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D001616:beta-Galactosidase