17.12.2012 Views

crc press - E-Lib FK UWKS

crc press - E-Lib FK UWKS

crc press - E-Lib FK UWKS

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Penetratins 33<br />

TABLE 2.3 (continued)<br />

Cargoes Internalized In Vitro and In Vivo<br />

with AntpHD-Derived Peptidic Vectors<br />

Type of cargo Length Vector Cargo effect Ref.<br />

PNA<br />

GalR1 21 mer Penetratin Down regulates Galanin receptor R1 in vivo 67<br />

Telomerase 13 mer Penetratin Inhibits telomerase in melanoma cells 65, 66<br />

Chemical drug<br />

Doxorubicin Penetratin Doxorubicin crosses BBB 78<br />

Cargo<br />

-SH<br />

Cargo -S-S- py<br />

Cargo<br />

NH2-<br />

Cargo<br />

-S-S-<br />

FIGURE 2.2 Two modes of coupling cargoes to Penetratin peptides: (1) linkage requiring<br />

disulfide bond formation. Cargo and vector are synthesized with a cysteine in which the thiol<br />

group is protected with a pyridinium group (py). The pyridinium on the cargo is removed<br />

either by dithiothreitol (DTT), in the case of oligonucleotides, or by tris-(2-carboxyethyl)<br />

phosphine hydrochloride (TCEP). (2) Chemical synthesis in tandem. The cargo (a peptide in<br />

this case) is synthesized in tandem with the vector. (3) Alternatively, fusion peptides (vector<br />

and cargo) can be ex<strong>press</strong>ed in E. Coli and purified.<br />

-S -<br />

NH2- Vector -COOH<br />

-S-S-<br />

Chemical synthesis and coupling via a disulfide bond<br />

Vector Cargo<br />

Chemical synthesis in tandem<br />

Vector Cargo<br />

Tandem synthesis in bacteria<br />

Vector<br />

py<br />

-COOH

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!