Trendbericht Biochemie 2017: Zellpenetration

Avrutina, Olga; Kolmar, Harald; Empting, Martin

doi:10.1002/nadc.20184071749

Cited by 1 publication

(3 citation statements)

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“…While a majority of CPP investigations deals with derivatives of natural products, such as Tat, Antp, and Penetratin, and with the artificial compounds oligo- l - and - d -arginines ( 1 ),[1 – 6][11 – 14] commonly specified as R n and r n , our work has focused on the unnatural oligo- β -arginines ( 2 , 3 in Figure 2) and their fluorescently[16 – 24] or radioactively[21] labeled and covalently modified[22] derivatives 3. They rapidly enter eukaryotic cells (3T3 mouse fibroblasts,[16][19] HeLa cells,[17] HEK293 cells,[20] human hepatocytes, fibroblasts, macrophages, infected but not ‘healthy’ erythrocytes,[19] and Plasmodium falciparum , a eukaryotic microorganism[19]), as well as prokaryotic cells ( Bacillus megaterium , Escherichia coli );[18] they also penetrate deep into mouse skin,[17] just like the analogous α -peptidic oligo-arginines.…”

Section: Introductionmentioning

confidence: 99%

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

Grogg

Hilvert

Ebert

et al. 2018

Helvetica Chimica Acta

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

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Section: Introductionmentioning

confidence: 99%

“…Leroux , may be especially applicable to the field of cell penetration . For those who are able to read German we recommend the recent review by O. Avrutina , H. Kolmar , and M. Empting …”

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confidence: 99%