A Novel Cell-Penetrating Peptide Sequence Derived by Structural Minimization of a Snake Toxin Exhibits Preferential Nucleolar Localization

作者：Radis Baptista Gandhi; de la Torre Beatriz G; Andreu David^*

来源：Journal of Medicinal Chemistry, 2008, 51(22): 7041-7044.

DOI：10.1021/jm8009475

Structural simplification of a 42-residue venom peptide by N-to-C-terminal splicing led to two sequences [YKQCHKKG-GXKKGSG, 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 mu M. Enantio-1 did not translocate, suggesting that peptide uptake was receptor-mediated.

• 出版日期2008-11-27