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Activation of cell-penetrating peptide fragments by disulfide formation.

ABSTRACT: Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative analysis. After disulfide formation between two complementary CPP fragments, cellular uptake of the resulting conjugates was observed. As confirmed by in vitro experiments, the conjugated peptides showed uptake activity comparable to the native CPP sequences, while the truncated peptides were hardly active. Until now, this split CPP strategy has only been demonstrated for oligo-arginine CPPs, but here we demonstrate that it is also applicable to other cell-penetrating peptides. This wider applicability may help in the design of new activatable cell-penetrating peptides for, e.g., targeted drug delivery.

SUBMITTER: Tooyserkani R

PROVIDER: S-EPMC7497323 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Activation of cell-penetrating peptide fragments by disulfide formation.

Tooyserkani Raheleh R Lipiński Wojciech W Willemsen Bob B Löwik Dennis W P M DWPM

Amino acids 20200731 8

Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative analysis. After disulfide formation between two complementary CPP fragments, cellular uptake of the resulting conjugates was observed. As confirmed by in vitro experiments, the conjugated peptides showed uptake activity comparable to the native ...[more]

PMID: 32737661

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