Cell Penetration, Herbicidal Activity, and in‐vivo‐Toxicity of Oligo‐Arginine Derivatives and of Novel Guanidinium‐Rich Compounds Derived from the Biopolymer Cyanophycin

摘要: Oligo-arginines are thoroughly studied cell-penetrating peptides (CPPs, Figures 1 and 2). Previous in-vitro investigations with the octaarginine salt of phosphonate fosmidomycin (herbicide anti-malaria drug) have shown a 40-fold parasitaemia inhibition P. falciparum, compared to alone (Figure 3). We now tested this salt, as well corresponding phosphinate herbicide glufosinate, for herbicidal activity whole plants by spray application, hoping increased activities, i.e. decreased doses. However, both salts showed low activity, indicating poor foliar uptake (Table 1). Another pronounced difference between in-vivo was demonstrated various fosmidomycin: intravenous injection mice caused exitus animals within minutes, even at doses 1.4 μmol/kg The results show that use CPPs drug delivery, instance cancer cells tissues, must be considered due care. biopolymer cyanophycin is poly-aspartic acid containing argininylated side chains 4); its building block dipeptide H-βAsp-αArg-OH (H-Adp-OH). To test compare biological properties those octaarginines we synthesized Adp8-derivatives 5). Intravenouse H-Adp8-NH2 into tail vein high 45 causes no symptoms whatsoever 3), but not cell penetrating (HEK293 MCF-7 cells, Figure 6). On other hand, fluorescently labeled octamers FAM-(Adp(OMe))8-NH2 FAM-(Adp(NMe2))8-NH2 ester amide groups in exhibit mediocre cell-wall permeability 6), toxic Possible reasons behavior discussed 7) NMR spectra presented 8).