Application of ESEM/Eds to Pharmaceutical Synthesis

1997 ◽  
Vol 3 (S2) ◽  
pp. 1201-1202
Author(s):  
R. A. Carlton ◽  
E. Orton ◽  
C. E. Lyman
Keyword(s):  
Solid Phase ◽  
Environmental Scanning Electron Microscopy ◽  
Solid Substrate ◽  
Biologically Active ◽  
Environmental Scanning ◽  
Phase Synthesis ◽  
Large Numbers ◽  
Unique Approach ◽  
Agricultural Industries ◽  
Active Substances

Solid phase synthesis (SPS) is used for the discovery and optimization of biologically active substances for the pharmaceutical and agricultural industries. Large numbers of novel organic compounds are generated by successively adding functional groups onto a solid substrate - usually polystyrene. Several techniques have been applied to the qualitative and quantitative analysis of these polymer-bound compounds with varying success. Environmental scanning electron microscopy (ESEM) with energy dispersive x-ray spectrometry (EDS) offers a unique approach to the qualitative analysis of SPS resins. Heteroatoms (such as Cl, Br, and S) are added either as a part of the synthesis or as a marker for analysis. Heavier atoms, such as these, are easily detected by EDS. The advantages of EDS are speed, sensitivity, and small required weight of the sample. The advantages of the ESEM are that it eliminates the need for a conductive coating and the vacuum conditions are not as severe on the specimen as with a conventional SEM.

PROSPECTS FOR OBTAINING FOOD INGREDIENTS AND BIOLOGICALLY ACTIVE SUBSTANCES FROM SUGAR BEET PULP

2021 ◽  
Author(s):  
С.О. СЕМЕНИХИН ◽  
В.О. ГОРОДЕЦКИЙ ◽  
Н.И. КОТЛЯРЕВСКАЯ ◽  
Е.П. ВИКТОРОВА ◽  
М.В. ЛУКЬЯНЕНКО
Keyword(s):  
Sugar Beet ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Sugar Beet Pulp ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Food Ingredients ◽  
Phase Synthesis ◽  
Beet Pulp ◽  
Active Substances

Представлен обзор зарубежных научных исследований по получению ванилина, олигосахаридов, липидов и ферментов из свекловичного жома. Наличие в составе свекловичного жома лигнина, состоящего в основном из феруловой кислоты, делает его перспективным источником для получения ванилина; по данным иранских исследователей его выход составляет 1439,3 мг/100 г свекловичного жома. В работах польских и нидерландских исследователей отмечено, что с применением различных ферментов можно достичь 95%-й степени гидролиза пищевых волокон свекловичного жома до олигосахаридов. При микробиологической обработке свекловичного жома для получения липидов их выработка составляет 0,12 г/г сухих веществ при длине цепи 16–18 атомов углерода, что аналогично длинам цепей липидов растительных масел. Микробиологический синтез ферментов из свекловичного жома также показал свою перспективность. Так, при жидкофазном ферментировании свекловичного жома с содержанием сухих веществ 2% выработка β-амилазы с применением P. chitinolyticus составила 2,237 ед./мл. При твердофазном синтезе β-глюкооксидазы с применением T. aurantiacus выработка составила 70 ед./г сухих веществ, а A. pullulans – 13 ед./г сухих веществ. При твердофазном синтезе α-галактозидазы плесенями A. niger выработка составила 230,159 ед./г сухих веществ, A. spinosa – 117,8 ед./г сухих веществ, F. moniliforme – 207,33 ед./г сухих веществ. Отмечено, что получаемые путем микробиологической обработки свекловичного жома ферменты обладают высокой активностью, а также устойчивостью к изменению температуры и реакции среды. Полученные различными исследователями данные показывают перспективность применения свекловичного жома для получения пищевых ингредиентов и биологически активных веществ. The article provides a review of foreign scientific research on the production of vanillin, oligosaccharides, lipids and enzymes from sugar beet pulp. The presence of lignin in beet pulp, mainly consisting of ferulic acid, makes it a promising source for vanillin obtaining – according to Iranian researchers, its yield is 1439,3 mg/100 g of sugar beet pulp. In the works of Polish and Dutch researchers, it was noted that using various enzymes it is possible to achieve a 95% degree sugar beet pulp dietary fiber hydrolysis to oligosaccharides. In the microbiological treatment of sugar beet pulp to produce lipids, their production is 0,12 g/g of dry substances with a chain length of 16–18 carbon atoms, which is similar to the vegetable oils lipid chains length. Microbiological synthesis of enzymes from beet pulp has also shown its prospects. So, with liquid-phase fermentation of sugar beet pulp with a dry substances content of 2%, the production of β-amylase using P. chitinolyticus was 2,237 units/ml. During solid-phase synthesis of β-glucooxidase using T. aurantiacus, it was 70 units/g of dry substances, and A. pullulans – 13 units/g of dry substances. During solid-phase synthesis of α-galactosidase by A. niger molds, production amounted to 230,159 units/g of dry substances, A. spinosa – 117,8 units/g of dry substances and F. moniliforme – 207,33 units/g of dry substances. It is noteworthy that the enzymes obtained by microbiological treatment of sugar beet pulp have high activity, as well as resistance to changes in temperature and the medium reaction. The data obtained by various researchers show the prospects of using beet pulp for the food ingredients and biologically active substances production.

The importance of linkers in the structure of PSMA ligands

2021 ◽  
Vol 28 ◽  
Author(s):  
Anastasia A. Uspenskaya ◽  
Ekaterina A. Nimenko ◽  
Aleksei E. Machulkin ◽  
Elena K. Beloglazkina ◽  
Alexander G. Majouga
Keyword(s):  
Prostate Cancer ◽  
Solid Phase ◽  
Biologically Active ◽  
Modern World ◽  
Synthesis Methods ◽  
Amino Acid Residues ◽  
Ongoing Research ◽  
Phase Synthesis ◽  
Diagnose Prostate Cancer ◽  
Positive Effect

: Cancer is one of the leading social problems of the modern world. Today prostate cancer is the second leading cause of cancer deaths among men. Targeted drug delivery is widely used to treat and diagnose prostate cancer. Conjugates selectively binding to prostate specific membrane antigen based on urea ligands are being actively developed against this disease. The linker has a significant influence on the biological activity of such conjugates. The linker performs a large number of functions, and its modification is one of the key methods of creating the best pharmacological profile. This review aims to discuss and analyze the main approaches to the method of introduction and synthesis of linkers for this type of conjugates without a description of the influence of biologically active molecules, as well as to establish the key modification methods that have a significant role on the structure-activity relationship. For this purpose, a review of the current scientific literature was performed, both for the conjugates under development and for those already undergoing clinical trials. It was found that the optimal structure is a linker containing an aliphatic fragment near the vector-molecule (n(CH2) = 3-6), followed by a polypeptide chain consisting of 2 to 4 amino acid residues. The presence of a Phe-Phe dipeptide chain or the introduction of negatively charged groups also has a positive effect. Ongoing research in this field helps to establish the accurate effect of each linker fragment, and the development of solid-phase synthesis methods makes it much easier to achieve this goal.

Manual multiple synthesis methods

1999 ◽  
Author(s):  
J. M. Ostresh ◽  
R. A. Houghten
Keyword(s):  
Polypropylene Mesh ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Phase Synthesis ◽  
Resin Beads ◽  
Large Numbers ◽  
Base Resin ◽  
Mesh Material ◽  
Antigen Interaction ◽  
Multiple Synthesis

Simultaneous multiple peptide synthesis enables the parallel synthesis of large numbers of peptides. The T-bag (tea-bag) method was developed along with other methods, e.g. pin synthesis, synthesis on paper plates, synthesis on parallel columns, and synthesis on cellulose, as technology to facilitate simultaneous multiple synthesis. Large numbers of peptides, peptidomimetics, and small organic molecules have been prepared using the T-bag method to address different research fields, such as conformational analysis, structure activity analysis, synthesis methodologies, and antibody-antigen interaction studies. Using the T-bag method, more than 150 peptides can be prepared in parallel in flexible amounts, with easily enough material for biological tests and analytical studies. The synthesis of peptides of length of up to 26 amino acid residues has been reported. Moreover, the T-bag technology is easy to apply in practice and requires very little special equipment. T-bags are prepared by containing solid phase resins within polypropylene mesh material. Polypropylene is rather chemically inert as well as fairly thermally stable (to 150°C), allowing a wide range of chemical reactions to be used for solid phase synthesis without affecting the bag material. Polystyrene cross-linked with 1% divinylbenzene, 100-200 mesh, is mainly used as the solid support, but other types of base resin can be used as well, e.g. TentaGel. The size of the resin beads must exceed the size of the pores of the polypropylene mesh material of the T-bags to avoid resin loss during synthesis. Syntheses are carried out manually, using semi automation, or within a multiple peptide synthesizer. The preparation of T-bags for solid phase synthesis, starting with 100 mg resin per bag, is described in Protocol 1. Synthesis using the T-bag method can be performed using either Boc or Fmoc synthetic strategies. For all manipulations, enough solvent should be used to cover the T-bags (about 3-4 ml per bag containing 100 mg of resin). To enable efficient washings and reactions, the reaction vessels (polyethylene bottles) should be shaken vigorously, preferably through the use of a reciprocating shaker.

scholarly journals Total Solid-Phase Synthesis of Biologically Active Drosophila Insulin-Like Peptide 2 (DILP2)

2017 ◽  
Vol 70 (2) ◽  
pp. 208 ◽  
Author(s):  
Feng Lin ◽  
Mohammed Akhter Hossain ◽  
Stephanie Post ◽  
Galina Karashchuk ◽  
Marc Tatar ◽  
...  
Keyword(s):  
Solid Phase ◽  
Cell Signalling ◽  
Fruit Fly ◽  
Total Solid ◽  
Biologically Active ◽  
Loss Of Function ◽  
Phase Synthesis ◽  
Function Relationship ◽  
G Protein Coupled ◽  
Synthesis Protocol

In the fruit fly Drosophila melanogaster, there are eight insulin-like peptides (DILPs) with DILPs 1–7 interacting with a sole insulin-like receptor tyrosine kinase (DInR) while DILP8 interacts with a single G protein-coupled receptor (GPCR), Lgr3. Loss-of-function dilp mutation studies show that the neuropeptide DILP2 has a key role in carbohydrate and lipid metabolism as well as longevity and reproduction. A better understanding of the processes whereby DILP2 mediates its specific actions is required. Consequently we undertook to prepare DILP2 as part of a larger, detailed structure–function relationship study. Use of our well established insulin-like peptide synthesis protocol that entails separate solid-phase assembly of each of the A- and B-chains with selective cysteine S-protection followed by sequential S-deprotection and simultaneous disulfide bond formation produced DILP2 in good overall yield and high purity. The synthetic DILP2 was shown to induce significant DInR phosphorylation and downstream signalling, with it being more potent than human insulin. This peptide will be a valuable tool to provide further insights into its binding to the insulin receptor, the subsequent cell signalling, and role in insect metabolism.

scholarly journals THE MAIN CONCEPTS OF SYNTHESIS OF PEPTIDES AS A NEW GENERATION OF BIOLOGICALLY ACTIVE DRUGS

2021 ◽  
Vol 58 ◽  
pp. 62-65
Author(s):  
Mikhail A. Polianskii ◽  
◽  
Anatoly I. Ginak ◽  
Keyword(s):  
Large Scale ◽  
Solid Phase ◽  
Biologically Active ◽  
Solid Polymer ◽  
Environmental Standards ◽  
Polymer Carrier ◽  
Phase Synthesis ◽  
Biological Targets ◽  
Living Organisms ◽  
New Generation

Currently, peptide-based drugs are increasingly replacing dosage forms which have been widely used for many years due to their affinity for living organisms and greater selectivity to biological targets, which lead to a growing demand. To meet that demand, a method using a solid polymer carrier (solid-phase synthesis), which has no alternative for fast and large-scale synthesis, is used. Nevertheless, work on its improvement is carried out non-stop, not only to optimize the chemical process, but also to bring the process to compliance with environmental standards dictated by modern concepts of green chemistry

scholarly journals The Analysis of Process of Crushing in the Vibrocavitational Homogenizer

2020 ◽  
Vol 9 (4) ◽  
pp. 53-58
Author(s):  
E. V. Flisyuk ◽  
S. S. Belokurov ◽  
I. A. Narkevich ◽  
O. M. Flisyuk ◽  
D. Yu. Ivkin
Keyword(s):  
Solid Phase ◽  
Raw Materials ◽  
Rotation Frequency ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Rotor Speed ◽  
Particle Crushing ◽  
Fenugreek Seeds ◽  
Average Probability ◽  
Active Substances

Introduction. Vibration cavitation homogenizers are increasingly used in various industries, including the pharmaceutical industry – for the preparation of creams, gels to give them a homogeneous composition, and more recently for the extraction of valuable substances from plant materials. As we have shown earlier, a comparison of the extraction of dioscin from fenugreek seeds, carried out in devices of various designs, under the same conditions for organizing the process showed that the most effective method was the extraction method in a vibro-cavitation field. Obviously, this is due to the fact that cavitation reduces the diffusion resistance of the process and, thus, increases the intensity of the process of transferring the mass of a substance from the solid phase to the solution. However, the extraction process in apparatus of this type is complex and is accompanied by crushing of seeds, which leads to a change in the dispersed composition of the solid phase.Aim. Conduct a theoretical and experimental analysis of the process of grinding hay fenugreek seeds particles in a vibrocavitation homogenizer, accompanied by the extraction of biologically active substances, as well as obtaining dependences that allow evaluating the contribution of grinding to the formation of the dispersed composition of the meal in this apparatus and determining the average particle size as a result of crushing. In earlier works, using the example of the extraction of dioscin from fenugreek seeds, it was shown that an increase in the rotor speed increases the yield of biologically active substances. However, fine grinding of raw materials often leads to the formation of a sediment layer that pollutes the solution with ballast substances and complicates its purification, and also reduces the yield of biologically active substances, therefore, the study of this process is necessary to control the dispersed composition in order to ensure the highest extraction efficiency in devices of this type.Materials and methods. The first stage of the study was the theoretical analysis of the grinding process, since it is a special case of a large class of processes in which the dispersed composition of the solid phase is not constant. Therefore, in this work, for the mathematical description of particle grinding, a model is used that takes into account the kinetic features of the process under consideration. An experimental study of the extraction of valuable components from plant raw materials was carried out in a laboratory setup with a vibro-cavitation homogenizer of periodic action. As a raw material, we used fenugreek seeds purchased from LLC «Stoing», Moscow (Russia), which we used for research. Commodity analysis showed the compliance of raw materials with the requirements of the GF XIV edition. The initial, aqueous solution of ethanol (volume concentration 60 %) with fenugreek seeds was loaded into glass 6, in a volume of 0.2 liters, then the rotor of the apparatus was brought into rotation and brought to a given rotation frequency. The experiments were carried out at a rotation frequency of 1000, 3000 and 5000 rpm (16.7; 50 and 83.3) 1/s. At each value of the rotor speed, the process time varied in the range from 0 to 50 minutes, and the process was carried out for 60, 120, 180, 240 and 300 seconds. Studies carried out for 5 minutes or more showed that the dispersed composition of the meal practically does not change over time, but significantly depends on the rotor speed. Thus, after 5 minutes, a certain stabilization of the dispersed composition occurs and further residence of the material in the apparatus does not lead to a noticeable change in the dispersed composition. After each experiment, the meal was taken, dried, and sieve analysis of the dispersed composition was carried out.Results and discussion. Based on the results obtained by processing the experimental data according to the equation, the values of the average probability of particle crushing were calculated and, as it turned out, it practically does not depend on time, but depends only on the rotor speed. The dependence of the change in the average probability of particle grinding at different rotor speed was obtained. The analysis of these results showed that the value of the average probability of particle grinding in the cavitation homogenizer increases with an increase in the rotor speed, which is quite expected, since the frequency of contacts of particles with the working organs of the apparatus increases. In addition, the obtained dependence for the average probability of particle crushing is linear. This Expression quite accurately describes the values of the change in time of the relative mass of particles in the working range n = 16.7 – 83.3 1/s. Taking these values into account, the experimental and calculated results are in good agreement.Conclusions. The proposed approach and the results obtained can be used to assess the dispersed composition of particles obtained in other designs of devices of similar action.

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