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26 Cell-Penetrating Peptides: Processes and Applications
TABLE 2.2
Internalization of Penetratin and Its Derivatives
Peptide Sequence Internalization
Similarly, to AntpHD, penetratin is internalized by an energy-independent mechanism
at both 4 and 37°C, has access to the cytoplasm and nucleus, from which it can
be retrieved without apparent degradation. 15 Translocation has been observed in all cell
types and in 100% of the cells. It is not concentration-dependent between 10 pM and
100 µM and, below 10 µM, toxicity is rare and cell-type dependent. Τhe presence of
three arginine and three lysine residues confers to the peptide an isoelectric point above
12. Finally, although penetratin can be represented under the form of an amphipathic
helix, circular dichroism experiments have shown that it is poorly structured in water
and adopts an α-helical structure only in a hydrophobic environment. 15
2.3 HOW DO PENETRATIN PEPTIDES CROSS
CELLULAR MEMBRANES?
Subcellular
distribution
43–58 RQIKIWFQNRRMKWKK +++ N > C
58–43 KKWKMRRNQFWIKIQR +++ N > C
D43–58 RQIKIWFQNRRMKWKK +++ N > C
Pro50 RQIKIWFPNRRMKWKK +++ N > C
3P RQPKIWFPNRRMPWKK +++ C > N
Met–Arg RQIKIWFQNMRRKWKK +++ N > C
7Arg RQIRIWFQNRRMRWRR +++ N > C
W/R RRWRRWWRRWWRRWRR +++ N > C
45–58 IKIWFQNRRMKWKK ++ N > C
52–58 RRMKWKK ++ N > C
48–58 WFQNRRMKWKK + N > C
47–58 IWFQNRRMKWKK + N > C
46–58 KIWFQNRRMKWKK + N > C
43–57 RQIKIWFQNRRMKWK – –
43–54 RQIKIWFQNRRM – –
2Phe RQIKIFFQNRRMKFKK – –
41–55 TERQIKIWFQNRRMK – –
46–60 KIWFQNRRMK – –
Penetratin internalization mechanisms were investigated through a chemical
approach. Two groups of data have emerged, gathered from structure and function
studies in biological systems and from biophysical and biochemical approaches in
purely artificial systems.
2.3.1 INFLUENCE OF STRUCTURAL PARAMETERS ON PEPTIDE TRANSLOCATION
Several derivatives from the original penetratin-1 sequence have been chemically
synthesized (Table 2.2). They were generated to address the following points. Is