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.

54 Cell-Penetrating Peptides: Processes and Applications<br />

TABLE 3.1<br />

Sequences and Uptake Parameters of Mastoparan (MP), Transportan (TP),<br />

and Transportan Analogues (TP2 to TP16)<br />

Length a Cellular uptake b<br />

Speed of<br />

uptake, τ0.5 Sequence (a.a.) 0°C 37°C (min)<br />

Galparan GWTLNSAGYLLGPINLKALAALAKKIL 27 nd nd nd<br />

TP GWTLNSAGYLLGK c INLKALAALAKKIL 27 +++ +++ 3.4<br />

TP2 GWTLNSAGYLLGK c INLKAKAALAKKLL 27 ++ ++<br />

TP3 C6H5CH2CO(D-Y(Me))FQNRPRYK c -(Ahx)<br />

-INLKALAALAKKIL ++ ++ nd<br />

TP4 GWTLNSAGYLLGK c FLPLILRKIVTAL 26 — — —<br />

TP5 GWTLNPAGYLLGK c INLKALAALAKKIL 27 + + nd<br />

TP6 GWTLNPPGYLLGK c INLKALAALAKKIL 27 + + nd<br />

TP7 ...LNSAGYLLGK c INLKALAALAKKIL 24 +++ +++ 4.3<br />

TP8 .........LLGK c INLKALAALAKKIL 18 — +/– —<br />

TP9 GWTLNSAGYLLGK c ..LKALAALAKKIL 25 +++ +++ 6.5<br />

TP10 ......AGYLLGK c INLKALAALAKKIL 21 +++ +++ 8.6<br />

TP11 GWTLNS......K c INLKALAALAKKIL 21 + + nd<br />

TP12 ...LNSAGYLLGK c ..LKALAALAKKIL 22 ++ ++ 10.7<br />

TP13 ...LNSAGYLLGK c ....ALAALAKKIL 20 — +/– —<br />

TP14 ......AGYLLGK c ..LKALAALAKKIL 19 ++ ++ nd<br />

TP15 ...LNSAGYLLGK c ..LKALAALAK… 19 — +/– —<br />

TP16 GWTLNSAGYLLGK c INLKAPAALAKKIL 27 — +/– —<br />

MP<br />

d<br />

INLKALAALAKKIL 14 + + nd<br />

a Number of amino acid residues.<br />

b Detection of biotin by indirect immunofluorescence: +++ denotes comparable, ++ or + decreased,<br />

and +/– weak uptake in relation to that of transportan.<br />

c Biotinylated at ε-amino group of Lys.<br />

d Biotinylated at the N terminus.<br />

strategy. The combination of these two peptides was motivated by the following<br />

observations:<br />

1. Galanin (1–13) had been shown to be the smallest fragment of this neuropeptide<br />

that exhibited a reasonably high affinity toward the galanin<br />

receptor type 1. 8<br />

2. Many chimeric galanin receptor ligands were shown to possess very high<br />

affinity to galanin receptors. They consisted of galanin (1–13) in N terminus<br />

and a fragment of other neuropeptide or just a stretch of hydrophobic<br />

amino acids in C terminus. 9<br />

3. The C-terminal part of the chimeras was suspected to interact primarily<br />

with cellular membranes rather than with the receptor protein. Therefore,<br />

mastoparan, known to interact with lipid membranes, was used to Cterminally<br />

extend galanin (1–13) in order to increase the affinity toward<br />

membranes. 7

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

Saved successfully!

Ooh no, something went wrong!