NMR and CD conformational studies of bradykinin and its agonists and antagonists: application to receptor binding

Most physiological processes are regulated by peptides that perform their functions by interacting with specific receptors on cells. Specific conformations of the peptides are required for correct interactions to take place, and a knowledge of the biologically important conformation is vital for the understanding of biological function. Over the last few years extensive studies using nuclear magnetic resonance and circular dichroism have been carried out on bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) and its antagonists with the objective of developing new drugs to combat severe pathologies associated with its production. In the present review, these techniques for the determination of peptide conformation are reviewed and applied to the study of bradykinin and its antagonists. Modeling of these conformational data in the presence of the B2 receptor or an antibody allows the biologically active conformations to be deduced and these are presented in this review.Key words: bradykinin antagonists, conformational analysis, NMR, CD, B2 receptor binding.

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Methods of peptide conformation studies.

Acta Biochimica Polonica ◽

10.18388/abp.2001_3870 ◽

2001 ◽

Vol 48 (4) ◽

pp. 1091-1099 ◽

Cited By ~ 9

Author(s):

A Bierzyński

Keyword(s):

Hydrogen Exchange ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Peptide Conformation ◽

Short Review ◽

Experimental Methods ◽

Conformational Space ◽

Conformational Studies ◽

Leading Role

In solution most of the peptides assume multiple flexible conformations. Determination of the dominant conformers and evaluation of their populations is the aim of peptide conformation studies, in which theoretical and experimental methods play complementary roles. Molecular dynamics or Monte Carlo methods are quite effective in searching the conformational space accessible to a peptide but they are not able to estimate, precisely enough, the populations of various conformations. Therefore, they must be supplemented by experimental data. In this paper, a short review of the experimental methods, most widely used in peptide conformational studies, is presented. Among them NMR plays the leading role. Valuable information is also obtained from hydrogen exchange, fluorescence resonance energy transfer, and circular dichroism measurements. The advantages and shortcomings of these methods are discussed.

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DETERMINATION OF AMINO ACIDS AND SUGARS CONTENT IN ANTENNARIA DIOICA GAERTN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.33909 ◽

2019 ◽

pp. 39-43 ◽

Cited By ~ 2

Author(s):

LIUDMYLA SLOBODIANIUK ◽

LILIIA BUDNIAK ◽

SVITLANA MARCHYSHYN ◽

ROXOLANA BASARABA

Keyword(s):

Amino Acids ◽

Free Amino ◽

Hplc Method ◽

Biologically Active Substances ◽

Biologically Active ◽

New Drugs ◽

Raw Material ◽

Primary Metabolites ◽

Active Substances

Objective: The purpose of our study was to determine sugars and amino acids content of Antennaria dioica Gaertn. herb. In continuation of the investigation of biologically active substances from Antennaria dioica Gaertn., it advisable to study the qualitative composition and quantitative contents of sugars and amino acids from the herb of this plant. Methods: The herb of Antennaria dioica Gaertn. was analyzed for the content of sugars by GC/MS. The amino acids were identified and quantified by HPLC method. Results: The results of GC/MS analysis showed that in Antennaria dioica Gaertn. herb D-glucose had the highest content (7.16±0.09) mg/g, followed by D-fructose (5.27±0.06) mg/g and D-saccharose (6.72±0.08) mg/g. In the raw material a large amount of monosaccharides derivative–Myo-inositol was revealed, a content of which was (2.12±0.06) mg/g. We determined 17 bound and 16 free amino acids in the Antennaria dioica Gaertn. by HPLC method. Conclusion: The contents of primary metabolites provide opportunities for creating medicine and food supplements. The results show that Antennaria dioica Gaertn. is a rich source of these important biologically active substances. The resulting data will be used with the further purpose to produce new drugs of natural origin.

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Fast Method for the Determination of Residual Solvents in Radiopharmaceutical Products

Revista de Chimie ◽

10.37358/rc.17.4.5526 ◽

2017 ◽

Vol 68 (4) ◽

pp. 666-670 ◽

Cited By ~ 1

Author(s):

Mirela Mihon ◽

Catalin Stelian Tuta ◽

Alina Catrinel Ion ◽

Dana Niculae ◽

Vasile Lavric

Keyword(s):

Gas Chromatography ◽

Control Method ◽

Limit Of Detection ◽

The Body ◽

Biologically Active ◽

Injection Technique ◽

Fast Method ◽

Residual Solvent ◽

Residual Solvents

The aim of this work was the development and validation of a fast analytical method to determine the residual solvents content in radiopharmaceuticals such as: 18F-Fluorodeoxyglucose (18F-FDG), 18F-Fluoroestradiol (18F-FES), 18F-Fluorothymidine (18F-FLT),18F-Fluoromisonidazole (18F-FMISO). Radiopharmaceuticals are radioactive preparations for medical purposes used in nuclear medicine as tracers in diagnostic imaging and treatment of certain diseases. Positron Emission Tomography (PET) is a medical imaging technique that consists in introducing into the body of a small amount of a biologically active chemical compound labelled with a short lived positron-emitting radioisotope (18F, 11C, 68Ga). Residual solvents are critical impurities in radiopharmaceuticals that can affect labelling, stability and physicochemical properties of drugs. Therefore, the determination of these solvents is essential for quality control of radiopharmaceuticals. Validation of the control method for residual solvents by gas chromatography is referred by the European Pharmacopoeia using a special injection technique (head space). The parameters of the method, which comply with International Conference on Harmonization guidelines, are: accuracy, precision, linearity, limit of detection, limit of quantification and robustness. The proposed method (direct gas chromatography injection) proved to be linear, precise, accurate and robust. Good linearity was achieved for all the solvents and correlation coefficients (R2) for each residual solvent were found more than 0.99.

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Oxazole-Based Compounds As Anticancer Agents

Current Medicinal Chemistry ◽

10.2174/0929867326666181203130402 ◽

2020 ◽

Vol 26 (41) ◽

pp. 7337-7371 ◽

Cited By ~ 3

Author(s):

Maria A. Chiacchio ◽

Giuseppe Lanza ◽

Ugo Chiacchio ◽

Salvatore V. Giofrè ◽

Roberto Romeo ◽

...

Keyword(s):

Cancer Research ◽

Drug Discovery ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Chemical Diversity ◽

Biologically Active ◽

New Drugs ◽

The Core ◽

Anti Cancer ◽

Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

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An Improved Methodology for Determination of Fluorine in Biological Samples Using High-Resolution Molecular Absorption Spectrometry via Gallium Fluorine Formation in a Graphite Furnace

Applied Sciences ◽

10.3390/app11125493 ◽

2021 ◽

Vol 11 (12) ◽

pp. 5493

Author(s):

Andrzej Gawor ◽

Andrii Tupys ◽

Anna Ruszczyńska ◽

Ewa Bulska

Keyword(s):

High Resolution ◽

Limit Of Detection ◽

Graphite Furnace ◽

Absorption Spectrometry ◽

Biological Tissues ◽

Biologically Active ◽

Molecular Absorption ◽

Biological Origin ◽

Molecular Absorption Spectrometry

Nowadays growing attention is paid to the control of fluorine content in samples of biological origin as it is present in the form of various biologically active organic compounds. Due to the chemically-rich matrix of biological tissues, the determination of fluorine becomes a very difficult task. Furthermore, a required complex sample preparation procedure makes the determination of the low contents of F by ion chromatography UV-Vis or ion-selective electrodes not possible. High-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) seems to be the best option for this purpose due to its high robustness to matrix interferences, especially in the presence of carefully selected modifiers. In this work the possibility of quantitative F determination in water and animal tissues was examined by measuring the molecular absorption of gallium monofluoride (GaF) at 211.248 nm with the use of a commercially available HR-CS GF MAS system. Experimental conditions for the sensitive and precise determination of fluorine were optimized, including the time/temperature program as well as addition of gallium and modifier mixture in combined mode. Under these conditions the fluoride present in the sample was stabilized up to 600 °C, and the optimum vaporization temperature for GaF was 1540 °C. Palladium and zirconium deposited onto the graphite surface served as solid modifiers; sodium acetate and ruthenium modifiers were added directly to the sample. The limit of detection and the characteristic mass of the method were 0.43 μg/L and 8.7 pg, respectively. The proposed procedure was validated by the use of certified reference materials (CRMs) of lake water and animal tissue; the acceptable recovery was obtained, proving that it can be applied for samples with a similar matrix.

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In vitro potency determination of botulinum neurotoxin B based on its receptor-binding and proteolytic characteristics

Toxicology in Vitro ◽

10.1016/j.tiv.2016.03.011 ◽

2016 ◽

Vol 34 ◽

pp. 97-104 ◽

Cited By ~ 7

Author(s):

Emina Wild ◽

Ursula Bonifas ◽

Jolanta Klimek ◽

Jan-Hendrik Trösemeier ◽

Beate Krämer ◽

...

Keyword(s):

Receptor Binding ◽

Botulinum Neurotoxin ◽

Botulinum Neurotoxin B

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What Can Electrochemical Methods Offer in Determining DNA–Drug Interactions?

Molecules ◽

10.3390/molecules26113478 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3478

Author(s):

Sandra Ramotowska ◽

Aleksandra Ciesielska ◽

Mariusz Makowski

Keyword(s):

Dna Sequences ◽

Electrode Materials ◽

High Reliability ◽

Electrochemical Methods ◽

Biologically Active ◽

New Drugs ◽

Binding Modes ◽

Voltammetric Techniques ◽

Experimental Approaches ◽

Cellular Dna

The interactions of compounds with DNA have been studied since the recognition of the role of nucleic acid in organisms. The design of molecules which specifically interact with DNA sequences allows for the control of the gene expression. Determining the type and strength of such interaction is an indispensable element of pharmaceutical studies. Cognition of the therapeutic action mechanisms is particularly important for designing new drugs. Owing to their sensitivity, simplicity, and low costs, electrochemical methods are increasingly used for this type of research. Compared to other techniques, they require a small number of samples and are characterized by a high reliability. These methods can provide information about the type of interaction and the binding strength, as well as the damage caused by biologically active molecules targeting the cellular DNA. This review paper summarizes the various electrochemical approaches used for the study of the interactions between pharmaceuticals and DNA. The main focus is on the papers from the last decade, with particular attention on the voltammetric techniques. The most preferred experimental approaches, the electrode materials and the new methods of modification are presented. The data on the detection ranges, the binding modes and the binding constant values of pharmaceuticals are summarized. Both the importance of the presented research and the importance of future prospects are discussed.

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