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Novel Cell‐Penetrating Peptides Based on α‐Aminoxy Acids
Author(s) -
Ma Yilong,
Yang Dongmei,
Ma Yan,
Zhang YuHui
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100682
Subject(s) - amino acid , endosome , cytosol , chemistry , peptide , biophysics , in vivo , cell penetrating peptide , cell , biochemistry , transporter , combinatorial chemistry , biology , enzyme , gene , microbiology and biotechnology
The remarkable ability of cell‐penetrating peptides (CPPs) to deliver cell‐impermeable compounds into living cells makes them attractive transporters for use in biology and medicine. Despite their highly efficient cellular uptake, CPPs consisting of natural amino acids always suffer from degradation and endosomal entrapment, thereby greatly limiting their application in vivo. Here, we describe the preparation of novel CPPs incorporating α‐aminoxy acid residues and their cellular uptake behavior. We demonstrate that introducing α‐aminoxy acids into the backbones of CPPs enhances their diffuse cytosolic distribution after direct membrane translocation. We also reveal a hybrid peptide, consisting of D ‐α‐aminoxy acids and L ‐α‐amino acids, that achieves efficient diffuse distribution in the cytosol, is stable toward serum, and possesses low cytotoxicity, thus making it a possible vector candidate for in vivo applications. Our results confirm that α‐aminoxy acids are useful building blocks when designing novel CPPs possessing favorable properties.