A novel cell-penetrating peptide sequence derived by structural minimization of a snake toxin exhibits preferential nucleolar localization.
Structural simplification of a 42-residue venom peptideby N-to-C-terminal splicing led to two sequences [YKQCHKKGGXKKGSG, where X = nil (1) or 6-aminohexanoyl (2)], both efficiently uptaken by HeLa cells and, most interestingly, specifically localized at the nucleolus. Retro-2 was uptaken less efficiently, but a single (His --> Ile) replacement recovered the translocation ability. None of the peptides were cytotoxic up to 100 microM. Enantio-1 did not translocate, suggesting that peptide uptake was receptor-mediated.
Rádis-Baptista
Gandhi
G
Department of Experimental and Health Sciences, Pompeu Fabra UniVersity, Dr Aiguader, 80, E-08003 Barcelona, Spain.
de la Torre
Beatriz G
BG
Andreu
David
D
D000595:Amino Acid Sequence; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012910:Snake Venoms / Q000737:chemistry*
D009842:Oligopeptides; D012910:Snake Venoms