Prediction of Cell-Penetrating Peptides |
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Authors: | Mattias?H?llbrink Kalle?Kilk Anna?Elmquist Pontus?Lundberg Maria?Lindgren Yang?Jiang Margus?Pooga Ursel?Soomets Email author" target="_blank">ülo?LangelEmail author |
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Institution: | (1) Department of Neurochemistry and Neurotoxicology, Stockholm University, S-106 91 Stockholm, Sweden;(2) Estonian Biocenter, Tartu, Estonia;(3) Department of Biochemistry, Tartu University, Tartu, Estonia |
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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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Keywords: | Cellular uptake cell-penetrating peptides |
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