A review of methods to synthesise 4′-substituted nucleosides

2014 ◽  
Vol 12 (46) ◽  
pp. 9291-9306 ◽  
Author(s):  
Mark Betson ◽  
Nigel Allanson ◽  
Philip Wainwright
Keyword(s):  
Scientific Community ◽  
Therapeutic Agents ◽  
Molecular Probes ◽  
Modified Nucleosides ◽  
Diagnostic Tools

Modified nucleosides have received a great deal of attention from the scientific community, either for use as therapeutic agents, diagnostic tools, or as molecular probes.

scholarly journals Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

2021 ◽  
Vol 17 ◽  
pp. 2680-2715
Author(s):  
Umesh P Aher ◽  
Dhananjai Srivastava ◽  
Girij P Singh ◽  
Jayashree B S
Keyword(s):  
Scientific Community ◽  
Therapeutic Agents ◽  
Molecular Probes ◽  
Modified Nucleosides ◽  
Nucleoside Analogues ◽  
Comprehensive Overview ◽  
Simple Modification ◽  
The Third ◽  
Effective Synthesis ◽  
Methylene Group

Sugar-modified nucleosides have gained considerable attention in the scientific community, either for use as molecular probes or as therapeutic agents. When the methylene group of the ribose ring is replaced with a sulfur atom at the 3’-position, these compounds have proved to be structurally potent nucleoside analogues, and the best example is BCH-189. The majority of methods traditionally involves the chemical modification of nucleoside structures. It requires the creation of artificial sugars, which is accompanied by coupling nucleobases via N-glycosylation. However, over the last three decades, efforts were made for the synthesis of 1,3-oxathiolane nucleosides by selective N-glycosylation of carbohydrate precursors at C-1, and this approach has emerged as a strong alternative that allows simple modification. This review aims to provide a comprehensive overview on the reported methods in the literature to access 1,3-oxathiolane nucleosides. The first focus of this review is the construction of the 1,3-oxathiolane ring from different starting materials. The second focus involves the coupling of the 1,3-oxathiolane ring with different nucleobases in a way that only one isomer is produced in a stereoselective manner via N-glycosylation. An emphasis has been placed on the C–N-glycosidic bond constructed during the formation of the nucleoside analogue. The third focus is on the separation of enantiomers of 1,3-oxathiolane nucleosides via resolution methods. The chemical as well as enzymatic procedures are reviewed and segregated in this review for effective synthesis of 1,3-oxathiolane nucleoside analogues.

Marine Biotechnology: Realizing the Potential

2007 ◽  
Vol 41 (3) ◽  
pp. 24-31 ◽  
Author(s):  
Shirley A. Pomponi ◽  
Daniel G. Baden ◽  
Yonathan Zohar
Keyword(s):  
Harmful Algal Bloom ◽  
Health Indicators ◽  
Marine Species ◽  
Molecular Probes ◽  
Microbial Pathogens ◽  
Cancer Drug ◽  
Diagnostic Tools ◽  
Human Consumption ◽  
Efficient Production ◽  
Marine Biotechnology

Marine biotechnology is an applied science, the goal of which is to develop goods and services from marine organisms and processes. The new wave of marine biotechnology research began in the early 1980s and includes some significant success stories. A new drug to manage pain is commercially available, and a new cancer drug has been recommended for approval, the first from a fish-eating snail and the second from a mangrove tunicate. Enzymes from hydrothermal vent microbes are routinely used in PCR reactions, and marine-derived molecular probes are helping understand the molecular basis of disease processes. Advances in aquaculture biotechnology have resulted in more efficient production of finfish and shellfish for human consumption, and polyunsaturated fatty acids from marine microalgae are used as nutritional supplements for adults and infants. Rapid diagnostic tools have been developed to monitor toxins in the environment and in seafood, and genetic fingerprinting techniques are helping to control illegal trade of threatened marine species. In the future, multidisciplinary programs in oceans and human health should focus not only on microbial pathogens and harmful algal bloom toxins but also on discovery of new chemicals to prevent or treat human diseases. And the development of biological and biochemical sensors to detect pathogens, contaminants, and toxins and to monitor human and environmental health indicators in the marine environment should be a very high priority in the establishment of U.S. coastal ocean observing systems.

scholarly journals Elucidating the druggable interface of protein−protein interactions using fragment docking and coevolutionary analysis

2016 ◽  
Vol 113 (50) ◽  
pp. E8051-E8058 ◽  
Author(s):  
Fang Bai ◽  
Faruck Morcos ◽  
Ryan R. Cheng ◽  
Hualiang Jiang ◽  
José N. Onuchic
Keyword(s):  
Drug Design ◽  
Protein Interactions ◽  
Binding Sites ◽  
Hot Spots ◽  
Therapeutic Agents ◽  
Molecular Probes ◽  
Therapeutic Drug ◽  
Protein Protein Interactions ◽  
Protein Surface ◽  
Fragment Docking

Protein−protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein−protein interfaces. (i) This method explores the binding of fragment-sized molecular probes on the protein surface using a molecular docking-based screen. (ii) The energetically favorable binding sites of the probes, called hot spots, are spatially clustered to map out candidate binding sites on the protein surface. (iii) A coevolution-based interface interaction score is used to discriminate between different candidate binding sites, yielding potential interfacial targets for therapeutic drug design. This approach is validated for important, well-studied disease-related proteins with known pharmaceutical targets, and also identifies targets that have yet to be studied. Moreover, therapeutic agents are proposed by chemically connecting the fragments that are strongly bound to the hot spots.

Single-chain antibodies as diagnostic tools and therapeutic agents

2009 ◽  
Vol 101 (06) ◽  
pp. 1012-1019 ◽  
Author(s):  
Constantin von zur Muhlen ◽  
Dominik von Elverfeldt ◽  
Karlheinz Peter ◽  
Christoph Hagemeyer
Keyword(s):  
Clinical Importance ◽  
Recombinant Antibodies ◽  
Therapeutic Agents ◽  
Antibody Fragments ◽  
Diagnostic Tools ◽  
Development Programs ◽  
Single Chain ◽  
Biologically Relevant ◽  
Structure Selection ◽  
Single Chain Antibodies

SummaryOver three decades after the generation of the first mouse monoclonal antibodies by Kohler and Milstein, recombinant antibodies are the fastest growing class of therapeutic proteins. Furthermore, antibodies are key detection reagents in research and diagnostics. Technology improvements have provided several approaches to manufacturing human antibodies with high affinity for biologically relevant targets. Approximately 300 development programs for therapeutic antibodies have been reported in industrial and academic laboratories, and this clearly demonstrates the expectations towards antibody technology. Antibody fragments are a subclass with growing clinical importance. This review focuses on single-chain antibodies as one of the smallest possible format for recombinant antibodies and their use as diagnostic tools and therapeutic agents. We describe the structure, selection and production of single-chain antibodies. Furthermore, we review current applications of antibody fragments focusing on thrombus targeting using fibrin- and platelet-specific single-chain antibodies as well as describing novel noninvasive imaging approaches for the diagnosis of thrombosis and inflammation.

scholarly journals Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers

2019 ◽  
Vol 20 (13) ◽  
pp. 3272 ◽  
Author(s):  
Suet Yen Chong ◽  
Choon Keong Lee ◽  
Chenyuan Huang ◽  
Yi Hsuan Ou ◽  
Christopher J. Charles ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cardiovascular Diseases ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Intrinsic Activity ◽  
Diagnostic Tools ◽  
Alternative Source ◽  
Technological Advantage

Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.

Decifrare la bassa statura nei bambini

2021 ◽  
Vol 40 (3) ◽  
pp. 159-166
Author(s):  
Francesco Chiarelli ◽  
Valeria Castorani ◽  
Nella Polidori
Keyword(s):  
Short Stature ◽  
Therapeutic Agents ◽  
Diagnostic Tools ◽  
Timely Manner ◽  
Poor Growth ◽  
Genetic Causes ◽  
Novel Treatment ◽  
Management Paradigms ◽  
Underlying Pathology

Short stature is the most common cause of referral to paediatricians. Only a minority of children with short stature have an underlying pathology. Although well-established diagnostic and management paradigms do exist, recent advances in molecular technologies have significantly improved our understanding of the genetic causes of short stature. Therefore, after the exclusion of nutritional, hormonal, inflammatory or systemic disorders, or skeletal dysplasias and syndromes, genetic causes should be ever supposed and genetic evaluation considered. An appropriate diagnosis of short stature should be performed as early as possible and personalized treatment should be started in a timely manner. Novel treatment approaches have been also proposed both as diagnostic tools and as therapeutic agents to optimize the approach to short stature. Therefore, detailed characterization of children with poor growth is necessary to perform a tailored diagnostic and therapeutic workup with the aim to decipher the causes of short stature better.

scholarly journals Forming Future Teachers’ Communicative Competences through the Student Scientific Society Activities

2019 ◽  
pp. 66-84 ◽  
Author(s):  
Roman S. Nagovitsyn ◽  
Irina A. Golubeva
Keyword(s):  
Extracurricular Activities ◽  
Scientific Community ◽  
Educational Institution ◽  
Round Table ◽  
Research Problem ◽  
Diagnostic Tools ◽  
Future Teachers ◽  
Essay Writing ◽  
New Perspective ◽  
Theoretical Stage

Introduction. This article is devoted to the analysis of the process improving communicative qualities of graduates and future subject teachers through the integration of educational and extracurricular activities. The authors analyze main directions of implementation of interpersonal, group and organizational communication in teacher training. The purpose of the article is to substantiate the effectiveness of the program of developing communicative competences on the basis of project activities in the student scientific community by creating special diagnostic tools. Materials and Methods. As a methodological substantiation of the study, the competence approach is considered; the implementation of the latter, in conjunction with the systemic, innovation-technological, qualitative, activity-oriented and personality-oriented approaches, provides a higher qualitative level of vocational training of future teachers. At the theoretical stage of the study, the foreign and Russian pedagogical theory, practices, standards and solutions to the stated research problem were analyzed. To confirm the effectiveness of the experimental results, methods of mathematical statistical analysis were applied and a special diagnosis was created, compiled in accordance with the Professional Standard of the teacher based on content analysis of the contents of the answers, in terms of the availability of linguistic units of positive and negative connotations. The practical part of the research involved the student scientific community of the Pedagogical Institute. Results. Based on the created model for the content of the communicative competence of the future teacher, the author’s 72-hour program was developed for 6-month extra-curricular activities. It contained various forms of work: the implementation of brainstorming methods, communicative battles, a round table, essay writing, scientific stand-up, intellectual play, etc. The peculiarity of the program was that in each case, up to three roles were considered: coordinator, creative person, participant. The study presents a new perspective on the monitoring of the quality of education, in particular, the author’s diagnosis of analysis of communicative skills aimed at achieving goals of pedagogical activity . Discussion and Conclusion. Practical application of the provisions identified in the study on the integration of educational and extracurricular activities for the formation of communicative qualities of students can be realized in the organization of the educational and educational space of a higher educational institution of the pedagogical profile. The qualitative approach used in the study to analyze the labor intensity of educational disciplines in terms of counting credit units to estimate competencies can be applied as one of the indicators of monitoring basic educational programs. The study will be useful for teacher trainers wishing to improve the educational space of various learning or ganizations for this profile of training.

scholarly journals A collection of designed peptides to target SARS-Cov-2 – ACE2 interaction: PepI-Covid19 database

2020 ◽  
Author(s):  
Ruben Molina ◽  
Baldo Oliva ◽  
Narcis Fernandez-Fuentes
Keyword(s):  
Scientific Community ◽  
Therapeutic Agents ◽  
Spike Protein ◽  
Structural Basis ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Potential Impact ◽  
Novel Therapeutic

AbstractThe angiotensin-converting enzyme 2 is the cellular receptor used by SARS coronavirus SARS-CoV and SARS-CoV-2 to enter the cell. Both coronavirus use the receptor-binding domain (RBD) of their viral spike protein to interact with ACE2. The structural basis of these interactions are already known, forming a dimer of ACE2 with a trimer of the spike protein, opening the door to target them to prevent the infection. Here we present PepI-Cov19 database, a repository of peptides designed to target the interaction between the RDB of SARS-CoV-2 and ACE2 as well as the dimerization of ACE2 monomers. The peptides were modelled using our method PiPreD that uses native elements of the interaction between the targeted protein and cognate partner that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations that preserve the key interactions on the interface. PepI-Covid19 database provides an easy and convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic agents.

scholarly journals Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis

Glycobiology ◽  
2021 ◽  
Author(s):  
Irene Friligou ◽  
Jana Gassner ◽  
Dominic Knoblauch ◽  
Gabriele Kagerer ◽  
Franziska Popp ◽  
...  
Keyword(s):  
Host Cell ◽  
Therapeutic Agents ◽  
Hinge Region ◽  
Hek293 Cells ◽  
Diagnostic Tools ◽  
Glycosylation Pattern ◽  
Fab Fragment ◽  
Hek 293 ◽  
Glycan Analysis ◽  
293 Cells

Abstract Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years. Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling. In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region. However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts. Non-recombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage. In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression. Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures. The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs. O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for non-recombinant Rb-IgGs. Substitution of this threonine allowed an almost complete Fab fragment cleavage. Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.

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