TY - JOUR
T1 - Design and evaluation of variants of the protein transduction domain originated from translationally controlled tumor protein
AU - Kim, Moonhee
AU - Maeng, Jeehye
AU - Jung, Jaehoon
AU - Kim, Hyo Young
AU - Kim, Hwa Jung
AU - Kwon, Youngjoo
AU - Lee, Kyunglim
N1 - Funding Information:
This study was supported by a grant from the National Research Foundation of Korea Grant funded by the Korean Government ( 2009-0064401 and 2009-0071926 ), Seoul R&BD Program ( ST090801 ), and the NCRC program of MOST/KOSEF ( R15-2006-020 ).
PY - 2011/5/18
Y1 - 2011/5/18
N2 - Protein transduction domains (PTDs) have been successfully employed to deliver therapeutic cargos both in vitro and in vivo because of their cellular penetrating ability. We previously reported that a 10-amino acid peptide (MIIYRDLISH) derived from the NH2-terminus of human translationally controlled tumor protein (TCTP) functions as a PTD. TCTP-PTD is quite different from other well-known PTDs in its hydrophobic composition and structural character, and the sequence requirements for transduction remain unknown. To identify the role of each residue, we compared the cellular uptake of various deletion mutants and Ala substituents of TCTP-PTD. The results showed that the amino terminal residues and the hydrophobic nature of the peptide, with a minimal length of nine residues, were necessary for transduction. Based on the elucidated sequence requirements, we designed and evaluated variants to improve the efficiency and solubility through sequential modification of TCTP-PTD. During the optimization process, we also delineated the contribution of residues and the advantageous composition of sequences for cellular uptake.
AB - Protein transduction domains (PTDs) have been successfully employed to deliver therapeutic cargos both in vitro and in vivo because of their cellular penetrating ability. We previously reported that a 10-amino acid peptide (MIIYRDLISH) derived from the NH2-terminus of human translationally controlled tumor protein (TCTP) functions as a PTD. TCTP-PTD is quite different from other well-known PTDs in its hydrophobic composition and structural character, and the sequence requirements for transduction remain unknown. To identify the role of each residue, we compared the cellular uptake of various deletion mutants and Ala substituents of TCTP-PTD. The results showed that the amino terminal residues and the hydrophobic nature of the peptide, with a minimal length of nine residues, were necessary for transduction. Based on the elucidated sequence requirements, we designed and evaluated variants to improve the efficiency and solubility through sequential modification of TCTP-PTD. During the optimization process, we also delineated the contribution of residues and the advantageous composition of sequences for cellular uptake.
KW - Cellular uptake
KW - Cytotoxicity
KW - Protein transduction domain
KW - PTD-mediated delivery
KW - Translationally controlled tumor protein
UR - http://www.scopus.com/inward/record.url?scp=79955683308&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2011.03.007
DO - 10.1016/j.ejps.2011.03.007
M3 - Article
C2 - 21440624
AN - SCOPUS:79955683308
SN - 0928-0987
VL - 43
SP - 25
EP - 31
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
IS - 1-2
ER -