Vol 49, No 3 (2023)

In the 1960s and 1970s, the Institute of Chemistry of Natural Compounds developed a topochemical approach for designing new biologically active peptide compounds, the applicability of which to the creation of inhibitors and effective substrates of proteolytic enzymes was shown by the author of this review under the direct supervision of V.T. Ivanov. The next task was to establish the conformation of protein neurotoxins from snake venoms and to study the topography of their binding to the target, the nicotinic acetylcholine receptor (nAChR) from the electric organ of the Torpedo marmorata ray. With selectively labeled derivatives containing one fluorescent or spin label on established amino acid residues, neurotoxin residues in contact with nAChR were identified for the first time. Later, in collaboration with the laboratory of V.T. Ivanov, new analogues of α-conotoxins (peptide neurotoxins from poisonous mollusks Conus), were synthesized including their photoactivated derivatives, which showed the participation of all Torpedo nAChR subunits in the binding of α‑conotoxins. The final part of the review briefly presents the recent achievements of the Department of Molecular Neuroimmune Signaling (headed by V.I. Tsetlin) concerning the isolation and synthesis of new peptide and protein neurotoxins and the study of their mechanism of action.

In the era of the growing global threat of antibiotic resistance, antimicrobial peptides (AMPs) are considered as new generation drugs for treatment of various infectious diseases. In this review, AMPs are seen as an alternative to traditional antibiotics, many of which have already lost or are gradually reducing their effectiveness against a number of critically important pathogenic microorganisms. Recent outbreaks of secondary infections during the COVID-19 pandemic have increased the interest in AMPs due to an acute shortage of effective agents against bacterial and fungal infections. The review summarized current data on clinical studies of AMPs, assembled a list of developed drugs based on AMPs at various stages of clinical trials, highlighted the urgency of study of new AMPs, and systematized the most relevant clinical data and application of AMPs.

Studying of structure-function relationships between a chromophore and its protein environment plays a key role in photophysical engineering of fluorescent proteins (FPs), specifically, in the guided designing of their new variants with a higher fluorescence quantum yield (FQY). Known approaches to FQY increasing mostly rely on suppression of the excited state nonradiative processes, but no tools have been suggested for the tuning of the radiative rate constant (k_r), which is also a potentially “adjustable” value. Here, we propose an experimental approach in which the synthetic chromophore of FP models the “fixation” of the most important radiationless constants and allows monitoring of the fluorescence lifetime flexibility (as an indicator of the k_r value). As a proof-of-concept, we studied the time-resolved fluorescence behavior of the green and blue FP chromophore analogs in diverse chemical environments. The conformationally locked analog of the GFP chromophore in most cases showed monophasic fluorescence decay kinetics with a lifetime of 2.7–3.0 ns, thus adequately modeling the typical behavior of GFPs with the highest FQYs. Under the conditions of stimulated ionization of this chromophore, we observed increased (up to 4.3–4.6 ns) fluorescence lifetimes, which can be interpreted in terms of an increase in the radiative constant (k_r). The conformationally locked analog of the Sirius chromophore showed biexponential fluorescence decay kinetics, partly simulating the properties of the blue FPs. In an acetic acid solution, this compound exhibited distinct fluorescent properties (elevated fluorescence intensity with a major lifetime population of ~4 ns), which can be interpreted as the emission of an unusual cationic form of the chromophore.

A preparation of tert-butyl esters of amino acid is described that proceeds from protected amino acids and tert-butanol using anhydrous magnesium sulfate and an excess of boron trifluoride diethyl etherate as additional reagents. The method affords tert-butyl esters in good yields and a variety of amino acid side chains and substituents tolerate the reaction conditions.

H-(RADA)₄-OH peptide in water tends to form biolgels at physiological conditions. Thusly made scaffold is formed of fibrils resulted from peptides self-assembling. Fibrils have two external hydrophilic layers, while hydrophobic one is situated between of them. Bio gels by the H-(RADA)₄-OH peptides are considered to be a prominent source for designed extra cellular matrix aimed to cell cultures of different types. Little is known about detailed structure the filament structure and β-sheets peptide composition. We have designed and studied molecular dynamics of bi-layered protofilament structures with β-sheets formed of parallel or anti-parallel peptide chains. Method of molecular dynamics was used to study H-(RADA)₄-OH peptide complexes at 80 and 300 K. While the most stable peptide complex was found to consist of anti-parallel peptides, had the lowest free energy and the least deviation of atom coordinates, yet another stable structure of the peptide complex was identified as 24-mer of parallel peptides with two β-sheets placed in syn orientation. These results underlined the importance of factors, directing the initial stages of the H-(RADA)₄-OH peptide self-assembling in solution.