Abstract
Cell-penetrating peptides, CPPs, are used as delivery vectors for pharmacologically interesting substances, such as antisense oligonucleotides, proteins and peptides. We present a general principle for designing cell-penetrating peptides derived from naturally occurring proteins as well as from randomly generated polyamino acid sequences. Thereby, we introduce a novel pharmacological principle for identification of cell-penetrating peptides for which the applications can be numerous, including cellular transduction vectors and mimics of intracellular protein–protein interactions. The methods of identifying a CPP comprises assessing the averaged bulk property values of the defined sequence, and ensuring that they fall within the bulk property value interval obtained from the training set. Despite this simplistic approach, the search criteria proved useful for finding CPP properties in either proteins or random sequences. We have experimentally verified cell-penetrating properties of 10–20-mer peptides derived from naturally occurring proteins as well as from random poly-amino acids. We note that since CPPs can be found in part of the protein sequences that may govern protein interactions, it is possible to produce cell-penetrating protein agonists or antagonists.
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Abbreviations
- GLP-1:
-
glucagone like peptide-1
- AT1AR:
-
angiotensine 1A receptor
- D2(long):
-
dopamine 2 receptor (long)
- CGRP:
-
calcitonine gene related protein
- mGluR:
-
metabotrobic glutamate receptor
- hGalR1:
-
human galanin receptor type 1
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Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( https://creativecommons.org/licenses/by-nc/2.0 ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
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Hällbrink, M., Kilk, K., Elmquist, A. et al. Prediction of Cell-Penetrating Peptides. Int J Pept Res Ther 11, 249–259 (2005). https://doi.org/10.1007/s10989-005-9393-1
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DOI: https://doi.org/10.1007/s10989-005-9393-1