Syntheses of Cyanophycin Segments for Investigations of Cell-Penetration

^§ This author did all the experiments

Abstract

Novel guanidinium-rich oligopeptide derivatives R-[Adp(X)]₈-NH₂ are described, which consist of an octa-aspartic acid backbone with argininylated side chains that are derived from the biopolymer cyanophycin [H-(Adp)_n-OH]. The Fmoc-Adp(X,Pbf)-OH building blocks for solid-state peptide synthesis (SSPS) of Adp octamers were prepared from Fmoc-Arg(Pbf)-OH and Fmoc-Asp-OAll. Coupling on PAL resin provided four octamers with and without N-terminal fluorescent groups (FAM) and C-terminal amide groups. Milligram quantities of Adp-octamers were isolated after preparative HPLC purification. The structure of the novel guanidinium-rich oligomers is unique insofar as the side chains of the Asp₈-backbone include both a guanidino and a carboxylic acid group, the influence of which will be tested with the corresponding ester and amide derivatives that were synthesized in parallel. Unusual cell-penetrating properties of the Adp-octamers are expected.

Key words

guanidinium-rich oligopeptides - β³/α-Asp-Arg-dipeptide building block - biopolymer cyanophycin - solid-state peptide synthesis - cell-penetrating peptides

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