Unnatural amino acids in enzymes and proteins

New trends in chemistry induced by genetic engineering and genomic information are analyzed. Genomic information and bioinformatics make the identification of all molecular participants of biological processes possible. The methods of identification of enzymeactive sites from sequence data were demonstrated. The problems of "chemical proteomics" were formulated and analyzed. New biocatalytic processes based on a new generation of enzymes, including CO 2 reduction and enzyme fuel cell construction, are demonstrated. It was shown that in many reactions the enzymes are substantially more efficient in comparison with classical chemical catalysts. The creation of recombinant proteins from unnatural amino acids is demonstrated, and organisms containing such proteins are described. The new trends of proteomics and bioanalytical chemistry in the postgenomic era are discussed.

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“…The amino acid analysis data are presented in Fig. 5 [56]. It was established that a significant part (35-40 %) of phenyl-…”

Section: Fluoro-containing Proteins and Organismsmentioning

confidence: 93%

“…Some analogs could not be incorporated into the proteins because of the high specificity of the above-mentioned synthetase. Nevertheless, there are several main ways of unnatural amino acids' incorporation in protein structure [56].…”

Section: Fluoro-containing Proteins and Organismsmentioning

confidence: 99%

Postgenomic chemistry: New problems and challenges

Varfolomeyev

Алиев

Ефременко

2004

Pure and Applied Chemistry

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“…The use of the created biomimetics is aimed at their competition with the substituted molecules, which affects the metabolic activity and growth of fungal cells [105]. The well-known metabolomics of fungi enable developing of approaches to the decrease in fungal resistance and adaptation to various stress conditions (ionizing radiation, pH change, hypoxic stress, solar ultraviolet radiation, presence of toxic compounds, nutrient stress, oxidative stress, cold-heat stress) (Table 5) [17,89,[106][107][108][109][110][111][112][113].…”

Section: Biomimetics Of Metabolites With Effect On Growth and Metabol...mentioning

confidence: 99%

“…Target of action *Antifungal effect Formyl phloroglucinol meroterpenoids [106] Reducing of hyphae elongation and filamentation due to blocking of potential outflow of fungal substrates MIC50 (mg/L): C. albicans (8.7), C. glabrata (13.5) 4-fluorophenylalanine (FPA) [107] Incorporation in proteins and inhibition of cell growth In recent decades, considerable attention has been paid to the development of antimicrobial and antitumor agents in the form of natural and non-canonical amino acids derivatives [114,115]. It has been established that such unnatural amino acids can be incorporated by yeast cells into their proteins, which leads to a noticeable inhibition of cell growth (Table 5) [107]. It was shown, that up to 35-40% of phenylalanine can be replaced by its fluorine-containing analogue in cell biomass of yeast Saccharomyces cerevisiae.…”

Section: Biomimetics As Antifungalsmentioning

confidence: 99%

Various Biomimetics as Antifungals

Efremenko,

Aslanli,

Stepanov

et al. 2023

Preprint

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Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

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“…There is significant interest in the preparation of modified proteins containing unnatural amino acids, in particular, fluorinated amino acid analogues, and this is due, on the one hand, to the possibility of solving a number of fundamental problems related to the studies of protein structures as well as structure-property relationships, and, on the other hand, to the probable practical application of these proteins. [36,37,38] The replacement of amino acid residues in proteins by their analogues may give rise to proteins with new properties and, in particular, may favorably change the properties of well-known proteins toward their practical use. In particular, their lipophilicity, their substrate specificity, their stability, their pK a values, their in vivo availability and improved permeation capability through certain body barriers, as well as their temperature optimum of action and folding kinetics can be modified.…”

Section: Nhmentioning

confidence: 99%

Total Synthesis of Various Hormaomycin Analogues with Modified Amino Acid Residues

Raev¹

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AM 250 (250 MHz), Varian Unity 300 (300 MHz), Inova 500 (500 MHz), Inova 600 (600 MHz). 1 H chemical shifts are reported in ppm relative to residual peaks of deuterated solvents: δ (ppm) = 2.49 for [D 5 ]DMSO, 4.65 for HOD in D 2 O, 7.26 for CHCl 3 , 1.73 and 3.55 for [D 7 ]THF, 3.35 for CHD 2 OD. Higher-order NMR spectra were approximately interpreted as first-order spectra, if possible. For the characterization of the observed signal multiplicities the following abbreviations have been applied: s = singlet, d = doublet, t = triplet, q = quartet, quin = quintet, m = multiplet, as well as b = broad. 13 C NMR [additional DEPT (Distortionless Enhancement by Polarization Transfer) or APT (Attached Proton Test)]: Bruker AM 250 (62.9 MHz), AMX 300 (75.5 MHz) or Varian Unity 300 (75.5 MHz), Inova 500 (125.7 MHz), Inova 600 (125.7 MHz) instruments. 13 BORWIN HSS-2000, column Nucleodur ® C18 (250 mm × 20 mm, 5 µm, 100 Å), flow rate 18.0 ml/min. Optical rotations: Perkin-Elmer 241 digital polarimeter, 1-dm cell; optical rotation values are given in 10 -1 deg cm 2 g -1 ; concentrations (c) are given in g/100 mL. M.p.: Büchi 510 capillary melting point apparatus, uncorrected values. TLC: Macherey-Nagel pre-coated sheets, 0.25 mm Sil G/UV254. The chromatograms were viewed under UV light and/or by treatment with phosphomolybdic acid (10% in ethanol), or ninhydrine (0.2% in ethanol), or I 2 vapor. Column chromatography: Merck silica gel, grade 60, 230-400 mesh and Baker silica gel, 40-140 mesh. Elemental analyses: Mikroanalytisches Laboratorium des Instituts für Organische und Biomolekulare Chemie der Universität Göttingen.Starting materials: Anhydrous solvents were prepared according to standard methods by distillation over drying agents and were stored under nitrogen. All other solvents were distilled before use.All reactions were carried out with magnetic stirring and, when employing air-or moisturesensitive materials, in flame-dried glassware under argon or nitrogen. 7.General synthetic protocols Deprotection of N-Fmoc-protected peptides (GP 1)The respective protected peptide (1 mmol) was taken up with acetonitrile or THF (2 mL), diethylamine (2 mL) was added, and the resulting mixture left at ambient temperature for 40 min. All volatiles were evaporated under reduced pressure, the residue was taken up with toluene (2 × 5 mL), which was evaporated under reduced pressure to remove the last traces of diethylamine. The obtained crude N-deprotected peptide was directly used in the next condensation step. Peptide condensation step for the preparation of peptides using EDC/HOAt -mediated coupling (GP 2)EDC (1.03 mmol) and HOAt (1.05 mmol) were added to a cooled (4 °C) solution of the respective N-protected amino acid (1 mmol) in anhydrous CH 2 Cl 2 (3 mL). After 20 min, the solution of the appropriate crude N-deprotected peptide (0.97 mmol) and TMP (3 mmol) in

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Unnatural amino acids in enzymes and proteins

Cited by 15 publications

References 30 publications

Postgenomic chemistry: New problems and challenges

Postgenomic chemistry: New problems and challenges

Various Biomimetics as Antifungals

Total Synthesis of Various Hormaomycin Analogues with Modified Amino Acid Residues

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