On Classical r-Matrix for the Kowalevski Gyrostat on so(4)

We present the trigonometric Lax matrix and classical r-matrix for the Kowalevski gyrostat on so(4) algebra by using the auxiliary matrix algebras so(3,2) or sp(4).Comment: Published in SIGMA (Symmetry, Integrability and Geometry: Methods and Applications) at http://www.emis.de/journals/SIGMA

The most reactive amide as a transition-state mimic for cis-trans interconversion.

1-Azatricyclo[3.3.1.1(3,7)]decan-2-one (3), the parent compound of a rare class of 90°-twisted amides, has finally been synthesized, using an unprecedented transformation. These compounds are of special interest as transition-state mimics for the enzyme-catalyzed cis-trans rotamer interconversion of amides involved in peptide and protein folding and function. The stabilization of the amide group in its high energy, perpendicular conformation common to both systems is shown for the rigid tricyclic system to depend, as predicted by calculation, on its methyl group substitution pattern, making 3 by some way the most reactive known "amide".Financial assistance from Enamine Ltd. (www.enamine.net) is gratefully acknowledged. We also thank Dr. V. Stepanenko for valuable advice and encouragement which helped to find the nonstandard solutions to the synthetic problems, and Vitaliy Bilenko for drawing our attention to the instructive EI mass spectrum of compound 8.This is the final published version of the article, originally published in the Journal of the American Chemical Society, 2015, 137 (2), pp 926–93, DOI: 10.1021/ja511460

Nature of Fast Relaxation Processes and Spectroscopy of a Membrane-Active Peptide Modified with Fluorescent Amino Acid Exhibiting Excited State Intramolecular Proton Transfer and Efficient Stimulated Emission

A fluorescently labeled peptide that exhibited fast excited state intramolecular proton transfer (ESIPT) was synthesized, and the nature of its electronic properties was comprehensively investigated, including linear photophysical and photochemical characterization, specific relaxation processes in the excited state, and its stimulated emission ability. The steady-state absorption, fluorescence, and excitation anisotropy spectra, along with fluorescence lifetimes and emission quantum yields, were obtained in liquid media and analyzed based on density functional theory quantum-chemical calculations. The nature of ESIPT processes of the peptide’s chromophore moiety was explored using a femtosecond transient absorption pump-probe technique, revealing relatively fast ESIPT velocity (∼10 ps) in protic MeOH at room temperature. Efficient superluminescence properties of the peptide were realized upon femtosecond excitation in the main long-wavelength absorption band with a corresponding threshold of the pump pulse energy of ∼1.5 μJ. Quantum-chemical analysis of the electronic structure of the peptide was performed using the density functional theory/time-dependent density functional theory level of theory, affording good agreement with experimental data

Surgical treatment of trophoblastic disease. Modern concept and contradictions (literature review)

A review of studies on the comparison of the effectiveness of surgical treatment of malignant trophoblastic tumors before the start of standard chemotherapy and in terms of combination treatment is presented. According to Russian and foreign studies, surgical treatment is relevant for patients with primary or metastatic tumor resistance. The article presents the results of treatment of patients after various types of operations. The most common volume of surgery was a hysterectomy. The article also discusses the results of treatment of benign forms of trophoblastic disease. Surgical treatment of a malignant trophoblastic tumor before the start of standard chemotherapy was performed according to vital indications or in connection with a tumor determined by imaging methods. And the analysis carried out in Blokhin National Medical Research Center of Oncology showed expected prognoses for patients who underwent surgical treatment prior to the start of standard chemotherapy regimens. Such patients were admitted to the clinic with a resistant or disseminated form of the tumor. During their treatment, high-dose chemotherapy or additional surgical interventions were required, which significantly worsened the prognosis of the disease. In the opposite case, when removing a localized resistant primary tumor or its metastasis, in the postoperative period, chemotherapy was not carried out in connection with marker remission

In Vivo Behavior of the Antibacterial Peptide Cyclo[RRRWFW], Explored Using a 3-Hydroxychromone-Derived Fluorescent Amino Acid

Labeling biomolecules with fluorescent labels is an established tool for structural, biochemical, and biophysical studies; however, it remains underused for small peptides. In this work, an amino acid bearing a 3-hydroxychromone fluorophore, 2-amino-3-(2-(furan-2-yl)-3-hydroxy-4-oxo-4H-chromen-6-yl)propanoic acid (FHC), was incorporated in a known hexameric antimicrobial peptide, cyclo[RRRWFW] (cWFW), in place of aromatic residues. Circular dichroism spectropolarimetry and antibacterial activity measurements demonstrated that the FHC residue perturbs the peptide structure depending on labeling position but does not modify the activity of cWFW significantly. FHC thus can be considered an adequate label for studies of the parent peptide. Several analytical and imaging techniques were used to establish the activity of the obtained labeled cWFW analogues toward animal cells and to study the behavior of the peptides in a multicellular organism. The 3-hydroxychromone fluorophore can undergo excited-state intramolecular proton transfer (ESIPT), resulting in double-band emission from its two tautomeric forms. This feature allowed us to get insights into conformational equilibria of the labeled peptides, localize the cWFW analogues in human cells (HeLa and HEK293) and zebrafish embryos, and assess the polarity of the local environment around the label by confocal fluorescence microscopy. We found that the labeled peptides efficiently penetrated cancerous cells and localized mainly in lipid-containing and/or other nonpolar subcellular compartments. In the zebrafish embryo, the peptides remained in the bloodstream upon injection into the cardinal vein, presumably adhering to lipoproteins and/or microvesicles. They did not diffuse into any tissue to a significant extent during the first 3 h after administration. This study demonstrated the utility of fluorescent labeling by double-emission labels to evaluate biologically active peptides as potential drug candidates in vivo

Fast Amide Bond Cleavage Assisted by a Secondary Amino and a Carboxyl Group-A Model for yet Unknown Peptidases?

Unconstrained amides that undergo fast hydrolysis under mild conditions are valuable sources of information about how amide bonds may be activated in enzymatic transformations. We report a compound possessing an unconstrained amide bond surrounded by an amino and a carboxyl group, each mounted in close proximity on a bicyclic scaffold. Fast amide hydrolysis of this model compound was found to depend on the presence of both the amino and carboxyl functions, and to involve a proton transfer in the rate-limiting step. Possible mechanisms for the hydrolytic cleavage and their relevance to peptide bond cleavage catalyzed by natural enzymes are discussed. Experimental observations suggest that the most probable mechanisms of the model compound hydrolysis might include a twisted amide intermediate and a rate-determining proton transfer