RESUMEN
The Human Glycome Atlas (HGA) Project was launched in April 2023, spearheaded by three Japanese institutes: the Tokai National Higher Education and Research System, the National Institutes of Natural Sciences, and Soka University. This was the first time that a field in the life sciences was adopted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for a Large-scale Academic Frontiers Promotion Project. This project aims to construct a knowledgebase of human glycans and glycoproteins as a standard for the human glycome. A high-throughput pipeline for comprehensively analyzing 20,000 blood samples in its first five years is planned, at which time an access-controlled version of a human glycomics knowledgebase, called TOHSA, will be released. By the end of the final tenth year, TOHSA will provide a central resource linking human glycan data with other omics data including disease-related information.
RESUMEN
Biomolecules containing adenosine di- or triphosphate (ADP or ATP) are crucial for diverse biological processes. Synthesis of these biomolecules and development of their chemical probes are important to elucidate their functions. Enabling reproducible and high-yielding access to these ADP- and ATP-containing molecules via conventional P(III)-P(V) and P(V)-P(V) coupling reactions is challenging owing to water content in highly polar phosphate-containing substrates. Herein, we report an efficient and reliable method for protecting-group-free P(V)-P(V) coupling reaction through inâ situ activation of phosphates using hydrolysis-stable 2-[N-(2-methylimidazoyl)]-1,3-dimethylimidazolinium chloride (2-MeImIm-Cl), providing the corresponding electrophilic P(V) intermediates for subsequent nucleophilic attack using their coupling partners. This P(V)-P(V) coupling reaction proceeded even in a wet reaction medium and showed a broad substrate scope, accommodating protecting-group-free synthesis of ADP-ribose and nicotinamide adenine diphosphate analogs, ATP-containing biomolecules, and ADP-ribosyl peptides.
Asunto(s)
Adenosina Difosfato Ribosa , Adenosina Trifosfato , Adenosina Trifosfato/química , Adenosina Difosfato Ribosa/química , Hidrólisis , Adenosina Difosfato/química , Fosfatos de Dinucleósidos/química , Fosfatos de Dinucleósidos/síntesis química , Estructura MolecularRESUMEN
To accelerate the biological study and application of the diverse functions of glycosphingolipids (GSLs), the production of structurally defined GSLs has been greatly demanded. In this review, we focus on the recent developments in the chemical and chemoenzymatic synthesis of GSLs. In the chemical synthesis section, the syntheses based on glucosyl ceramide cassette, late-stage sialylation, and diversity-oriented strategies for GSLs or ganglioside synthesis are highlighted, which delivered terpioside B, fluorescent sialyl lactotetraosyl ceramide, and analogs of lacto-ganglio-series GSLs, respectively. In the chemoenzymatic synthesis section, the synthesis of ganglioside GM1 by multistep one-pot multienzyme method and the total synthesis of highly complex ganglioside LLG-5 using a water-soluble lactosyl ceramide as a key substrate for enzymatic sialylation are described.