Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives

10.26434/chemrxiv.13372289 ◽

2020 ◽

Author(s):

Emil Johansson ◽

Rémi Caraballo ◽

Mikael Elofsson

Keyword(s):

Drug Discovery ◽

Mammalian Cells ◽

Natural Compounds ◽

Neuraminic Acid ◽

Synthetic Analogs ◽

Acetylneuraminic Acid ◽

Health And Disease ◽

Alkylation Reactions

N-acetyl neuraminic acid (Neu5Ac) is a densely functionalized nine-carbon monosaccharide. It ubiquitously decorates the surface of mammalian cells were it is found in terminal positions of glycolipids and glycoproteins. This important saccharide and natural analogs play important roles in a number of processes in health and disease. Despite this few Neu5Ac based therapeutics have been developed. To further study and understand the chemistry and biology of Neu5Ac efficient protocols for synthesis of the parent natural compounds as well as synthetic analogs are required. In the manuscript, we report investigation of alkylation reactions to produce selectively modified Neu5Ac with focus on position 4. The study provides insights in the reaction and we establish robust protocols that allow selective modification of Neu5Ac for use as tool compounds and starting points for drug discovery.

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In Vitro Immunodetection of Prothymosin Alpha in Normal and Pathological Conditions

Current Medicinal Chemistry ◽

10.2174/0929867326666190807145212 ◽

2020 ◽

Vol 27 (29) ◽

pp. 4840-4854 ◽

Cited By ~ 2

Author(s):

Chrysoula-Evangelia Karachaliou ◽

Hubert Kalbacher ◽

Wolfgang Voelter ◽

Ourania E. Tsitsilonis ◽

Evangelia Livaniou

Keyword(s):

Mammalian Cells ◽

Therapeutic Potential ◽

Prothymosin Alpha ◽

Disease States ◽

Leading Role ◽

Tissue Extracts ◽

Biologic Response ◽

Health And Disease ◽

Almost All

Prothymosin alpha (ProTα) is a highly acidic polypeptide, ubiquitously expressed in almost all mammalian cells and tissues and consisting of 109 amino acids in humans. ProTα is known to act both, intracellularly, as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response modifier mediating immune responses similar to molecules termed as “alarmins”. Antibodies and immunochemical techniques for ProTα have played a leading role in the investigation of the biological role of ProTα, several aspects of which still remain unknown and contributed to unraveling the diagnostic and therapeutic potential of the polypeptide. This review deals with the so far reported antibodies along with the related immunodetection methodology for ProTα (immunoassays as well as immunohistochemical, immunocytological, immunoblotting, and immunoprecipitation techniques) and its application to biological samples of interest (tissue extracts and sections, cells, cell lysates and cell culture supernatants, body fluids), in health and disease states. In this context, literature information is critically discussed, and some concluding remarks are presented.

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Epigenetics, Nutrition, Disease and Drug Development

Current Drug Discovery Technologies ◽

10.2174/1570163815666180419154954 ◽

2019 ◽

Vol 16 (4) ◽

pp. 386-391 ◽

Cited By ~ 1

Author(s):

Kenneth Lundstrom

Keyword(s):

Dna Methylation ◽

Drug Discovery ◽

Rna Interference ◽

Nutritional Requirements ◽

Signal Pathways ◽

Disease Development ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Health And Disease ◽

Novel Drug

Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also the treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established. Therefore, in attempts to develop novel safer and more efficacious drugs, both nutritional requirements and epigenetic mechanisms need to be addressed.

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Partitioning Pattern of Natural Products Based on Molecular Properties Descriptors Representing Drug-Likeness

Symmetry ◽

10.3390/sym13040546 ◽

2021 ◽

Vol 13 (4) ◽

pp. 546

Author(s):

Miroslava Nedyalkova ◽

Vasil Simeonov

Keyword(s):

Natural Products ◽

Drug Discovery ◽

De Novo ◽

Target Prediction ◽

Natural Compounds ◽

Discovery Process ◽

Drug Discovery Process ◽

Unique Source ◽

The Times ◽

Partitioning Pattern

A cheminformatics procedure for a partitioning model based on 135 natural compounds including Flavonoids, Saponins, Alkaloids, Terpenes and Triterpenes with drug-like features based on a descriptors pool was developed. The knowledge about the applicability of natural products as a unique source for the development of new candidates towards deadly infectious disease is a contemporary challenge for drug discovery. We propose a partitioning scheme for unveiling drug-likeness candidates with properties that are important for a prompt and efficient drug discovery process. In the present study, the vantage point is about the matching of descriptors to build the partitioning model applied to natural compounds with diversity in structures and complexity of action towards the severe diseases, as the actual SARS-CoV-2 virus. In the times of the de novo design techniques, such tools based on a chemometric and symmetrical effect by the implied descriptors represent another noticeable sign for the power and level of the descriptors applicability in drug discovery in establishing activity and target prediction pipeline for unknown drugs properties.

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ChemInform Abstract: Enzymes in Carbohydrate Synthesis: N-Acetylneuraminic Acid Aldolase Catalyzed Reactions and Preparation of N-Acetyl-2-deoxy-D-neuraminic Acid Derivatives.

ChemInform ◽

10.1002/chin.198901259 ◽

1989 ◽

Vol 20 (1) ◽

Author(s):

M.-J. KIM ◽

W. J. HENNEN ◽

H. M. SWEERS ◽

C.-H. WONG

Keyword(s):

Neuraminic Acid ◽

Acetylneuraminic Acid ◽

Carbohydrate Synthesis ◽

Catalyzed Reactions

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Mitochondrial Iron in Human Health and Disease

Annual Review of Physiology ◽

10.1146/annurev-physiol-020518-114742 ◽

2019 ◽

Vol 81 (1) ◽

pp. 453-482 ◽

Cited By ~ 14

Author(s):

Diane M. Ward ◽

Suzanne M. Cloonan

Keyword(s):

Human Health ◽

Mammalian Cells ◽

Molecular Mechanisms ◽

Innate Immune ◽

Biological Functions ◽

Mitochondrial Homeostasis ◽

Innate Immune Signaling ◽

Mitochondrial Iron ◽

Health And Disease

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. In recent years, cellular and animal models of mitochondrial iron dysfunction have provided vital information in identifying new proteins that have elucidated the pathways involved in mitochondrial homeostasis and iron metabolism. Specific signatures of mitochondrial iron dysregulation that are associated with disease pathogenesis and/or progression are becoming increasingly important. Understanding the molecular mechanisms regulating mitochondrial iron pathways will help better define the role of this important metal in mitochondrial function and in human health and disease.

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TLR4 signalling in the intestine in health and disease

Biochemical Society Transactions ◽

10.1042/bst0351473 ◽

2007 ◽

Vol 35 (6) ◽

pp. 1473-1478 ◽

Cited By ~ 94

Author(s):

M. Fukata ◽

M.T. Abreu

Keyword(s):

Mammalian Cells ◽

Metabolic Energy ◽

Short Term ◽

Receptor Signalling ◽

Health And Disease ◽

Inflammatory Bowel ◽

Term Benefit ◽

Tlr Signalling

The colonic epithelium is lined along its apical membrane with ∼1014 bacteria/g of tissue. Commensal bacteria outnumber mammalian cells in the gut severalfold. The reason for this degree of commensalism probably resides in the recent recognition of the microbiome as an important source of metabolic energy in the setting of poorly digestible nutrients. As in many themes in biology, the host may have sacrificed short-term benefit, i.e. nutritional advantages, for long-term consequences, such as chronic inflammation or colon cancer. In the present review, we examine the role of TLR (Toll-like receptor) signalling in the healthy host and the diseased host. We pay particular attention to the role of TLR signalling in idiopathic IBD (inflammatory bowel disease) and colitis-associated carcinogenesis. In general, TLR signalling in health contributes to homoeostatic functions. These include induction of antimicrobial peptides, proliferation and wound healing in the intestine. The pathogenesis of IBD, ulcerative colitis and Crohn's disease may be due to increased TLR or decreased TLR signalling respectively. Finally, we discuss the possible role of TLR signalling in colitis-associated neoplasia.

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Kinetic studies on the acid hydrolysis of the methyl ketoside of unsubstituted and O-acetylated N-acetylneuraminic acid

Biochemical Journal ◽

10.1042/bj1330623 ◽

1973 ◽

Vol 133 (4) ◽

pp. 623-628 ◽

Cited By ~ 13

Author(s):

A. Neuberger ◽

Wendy A. Ratcliffe

Keyword(s):

Sialic Acid ◽

Acid Hydrolysis ◽

Model Compound ◽

Kinetic Studies ◽

Order Rate Constant ◽

Neuraminic Acid ◽

Acetylneuraminic Acid ◽

Rate Of Hydrolysis ◽

Ph Range ◽

Hydrolysis Of

The hydrolysis of the model compound 2-O-methyl-4,7,8,9-tetra-O-acetyl-N-acetyl-α-d-neuraminic acid and neuraminidase (Vibrio cholerae) closely resembled that of the O-acetylated sialic acid residues of rabbit Tamm–Horsfall glycoprotein. This confirmed that O-acetylation was responsible for the unusually slow rate of acid hydrolysis of O-acetylated sialic acid residues observed in rabbit Tamm–Horsfall glycoprotein and their resistance to hydrolysis by neuraminidase. The first-order rate constant of hydrolysis of 2-methyl-N-acetyl-α-d-neuraminic acid by 0.05m-H2SO4 was 56-fold greater than that of 2-O-methyl-4,7,8,9-tetra-O-acetyl-N-acetyl -α-d-neuraminic acid. Kinetic studies have shown that in the pH range 1.00–3.30, the observed rate of hydrolysis of 2-methyl-N-acetyl-α-d-neuraminic acid can be attributed to acid-catalysed hydrolysis of the negatively charged CO2− form of the methyl ketoside.

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