crc press - E-Lib FK UWKS

Penetratins 33
TABLE 2.3 (continued)
Cargoes Internalized In Vitro and In Vivo
with AntpHD-Derived Peptidic Vectors
Type of cargo Length Vector Cargo effect Ref.
PNA
GalR1 21 mer Penetratin Down regulates Galanin receptor R1 in vivo 67
Telomerase 13 mer Penetratin Inhibits telomerase in melanoma cells 65, 66
Chemical drug
Doxorubicin Penetratin Doxorubicin crosses BBB 78
Cargo
-SH
Cargo -S-S- py
Cargo
NH2-
Cargo
-S-S-
FIGURE 2.2 Two modes of coupling cargoes to Penetratin peptides: (1) linkage requiring
disulfide bond formation. Cargo and vector are synthesized with a cysteine in which the thiol
group is protected with a pyridinium group (py). The pyridinium on the cargo is removed
either by dithiothreitol (DTT), in the case of oligonucleotides, or by tris-(2-carboxyethyl)
phosphine hydrochloride (TCEP). (2) Chemical synthesis in tandem. The cargo (a peptide in
this case) is synthesized in tandem with the vector. (3) Alternatively, fusion peptides (vector
and cargo) can be expressed in E. Coli and purified.
-S -
NH2- Vector -COOH
-S-S-
Chemical synthesis and coupling via a disulfide bond
Vector Cargo
Chemical synthesis in tandem
Vector Cargo
Tandem synthesis in bacteria
Vector
py
-COOH