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An unexpected cell‐penetrating peptide from Bothrops jararaca venom identified through a novel size exclusion chromatography screening
Author(s) -
Sciani Juliana Mozer,
Vigerelli Hugo,
Costa André Santos,
Câmara Diana Aparecida Dias,
Junior Paulo LuizdeSá,
Pimenta Daniel Carvalho
Publication year - 2017
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2965
Subject(s) - bothrops jararaca , peptide , venom , chemistry , in vivo , biochemistry , cell penetrating peptide , size exclusion chromatography , in vitro , snake venom , biology , enzyme , microbiology and biotechnology
Efficient drug delivery systems are currently one of the greatest challenges in pharmacokinetics, and the transposition of the gap between in vitro candidate molecule and in vivo test drug is, sometimes, poles apart. In this sense, the cell‐penetrating peptides (CPP) may be the bridge uniting these worlds. Here, we describe a technique to rapidly identify unlabeled CPPs after incubation with liposomes, based on commercial desalting (size exclusion) columns and liquid chromatography‐MS/MS, for peptide de novo sequencing. Using this approach, we found it possible to identify one new CPP – interestingly, a classical bradykinin‐potentiating peptide – in the peptide‐rich low molecular mass fraction of the Bothrops jararaca venom, which was also able to penetrate live cell membranes, as confirmed by classical approaches employing fluorescence‐labeled analogues of this CPP. Moreover, both the labeled and unlabeled CPPs caused no metabolic, cell‐cycle or morphologic alterations, proving to be unmistakably cargo deliverers and not drugs themselves. In sum, we have developed and validated a method for screening label‐free peptides for CPP activity, regardless of their biological origin, which could lead to the identification of new and more efficient drug delivery systems. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.