Enzymatic Modification of Soluble Cyanophycin Using the Type II Peptidyl Arginine Deiminase from <i>Oryctolagus cuniculus</i>

Wiefel, Lars; Steinbüchel, Alexander

doi:10.1002/mabi.201500433

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…Modification of cyanophycin, a peptide polymer composed of N-arginyl-aspartate units, using type II peptidyl arginine deiminase from Oryctolagus cuniculus led to the conversion of arginine residues to citrulline [ 204 ].…”

Section: Biocatalytic Modification Of Polymersmentioning

confidence: 99%

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

Nikulin

Švedas

2021

Molecules

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Trends in the dynamically developing application of biocatalysis for the synthesis and modification of polymers over the past 5 years are considered, with an emphasis on the production of biodegradable, biocompatible and functional polymeric materials oriented to medical applications. The possibilities of using enzymes not only as catalysts for polymerization but also for the preparation of monomers for polymerization or oligomers for block copolymerization are considered. Special attention is paid to the prospects and existing limitations of biocatalytic production of new synthetic biopolymers based on natural compounds and monomers from biomass, which can lead to a huge variety of functional biomaterials. The existing experience and perspectives for the integration of bio- and chemocatalysis in this area are discussed.

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Section: Biocatalytic Modification Of Polymersmentioning

confidence: 99%

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

Nikulin

Švedas

2021

Molecules

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“…This reaction completely converted the lysine residues of CGP to homoarginine (Frommeyer et al 2014). The feasibility of enzymatic CGP modification was demonstrated by Wiefel and Steinbüchel (2016) using a peptidyl arginine deiminase from Oryctolagus cuniculus, which normally introduces post-translational modifications on several proteins, to catalyze the conversion of arginine residues to citrulline. The conversion rate was, however, only 7.5 mol% of the CGPs amino acids, likely due to product inhibition by the citrulline.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Modification of Bacterial Cyanophycin and Cyanophycin Dipeptides Using Chemical Agents Towards Novel Variants of the Biopolymer

et al. 2019

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Variations of the composition of cyanophycin (CGP) have been investigated since the early 2000s. Modifications of the polymer are of academical interest, but also expand the number of putative applications for CGP and its dipeptides in fields like food supplementations, and medical and cosmetic applications. Until recently variations of the composition occurred only in vivo. However, in the last years, two procedures using chemical or enzymatic in vitro modification were successfully applied. Since chemical treatments were more effective and reached higher conversion rates, a search for reagents and their applicability to conduct reactions with CGP was done. The reaction of CGP with methyl isocyanate resulted in the conversion of 50% of the lysine residues, while only 3% of the arginine residues were modified. However, using digested CGP dipeptides, the conversion rates of lysine increased slightly to 72%, while the conversion of arginine reached 96%. Using formaldehyde, CGP could be methylated with a conversion rate of 84% for lysine and 15% for arginine. Acetylation of lysine residues was obtained using acetic anhydride, reaching a conversion rate of 100% for a single acetylation, where 63% of the residues were acetylated twice. Arginine residues could be acetylated at a rate of 89%. Diacetyl could be added to 80% of all arginine residues, while lysine was not targeted by the compound. Other agents were also tested, but showed lesser or no conversion and/or inconclusive results. Overall, the tested reactions confirm the viability of chemical CGP modification for future approaches.

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“…There is, however, a peptidic biopolymer carrying an arginine side chain with a terminal guanidine group on each and every residue: cyanophycin ( Figure ), largely unknown among chemists, biochemists, and biologists. In view of our interest in GRCs we have followed the research of Alexander Steinbüchel and his group (University Münster) in the field of cyanophycin for years . This biopolymer has an intriguing structure: it is a poly‐aspartic‐acid N ‐argininylated on the carboxylic acid groups of the side chains ( Figure ).…”

Section: Introductionmentioning

confidence: 99%

“…Synthetases producing the polymer and cyanophycinases degrading it have been isolated and can be used for production of the polymer on technical scale. The building block of the polymer consisting of aspartic acid and arginin has been proposed as a di‐aminoacid‐nutrient additive; for leading papers on these subjects see the articles by the Steinbüchel group in refs . and publications cited therein.…”

Section: Introductionmentioning

confidence: 99%

“… The observation that the Adp‐octamer 10 has no i.v .‐toxicity matches well with the fact that the ‘monomer’ H‐Adp‐OH itself is being considered as a dipeptidic nutrient additive ( vide supra ), which means that it does not exhibit any p.o .‐toxicity. See publications cited in ref ,. especially those coauthored by A. Sallam ; type in Google: ‘Zwei Aminosäuren als Geschäftsidee.…”

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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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Enzymatic Modification of Soluble Cyanophycin Using the Type II Peptidyl Arginine Deiminase from Oryctolagus cuniculus

Cited by 9 publications

References 23 publications

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

In Vitro Modification of Bacterial Cyanophycin and Cyanophycin Dipeptides Using Chemical Agents Towards Novel Variants of the Biopolymer

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

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