Despite being a relatively new addition to the Omics' land-scape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical... Show moreDespite being a relatively new addition to the Omics' land-scape, lipidomics is increasingly being recognized as an important tool for the identification of druggable targets and biochemical markers. In this review we present recent ad-vances of lipid analysis in drug discovery and development. We cover current state of the art technologies which are constantly evolving to meet demands in terms of sensitivity and selectivity. A careful selection of important examples is then provided, illustrating the versatility of lipidomics analysis in the drug discovery and development process. Integration of lipi-domics with other omics', stem-cell technologies, and meta-bolic flux analysis will open new avenues for deciphering pathophysiological mechanisms and the discovery of novel targets and biomarkers. Show less
Supramolecular glycopolymers exhibiting inherent dynamicity, tunability, and adaptivity allow us to arrive at a deeper understanding of multivalent carbohydrate-carbohydrate interactions and... Show moreSupramolecular glycopolymers exhibiting inherent dynamicity, tunability, and adaptivity allow us to arrive at a deeper understanding of multivalent carbohydrate-carbohydrate interactions and carbohydrate-protein interactions, both being essential to key biological events. The impacts of the carbohydrate segments in these supramolecular glycopolymers towards their structure, dynamics, and function as biomaterials are addressed in this minireview. Bottlenecks and challenges are discussed, and we speculate about possible future directions. Show less
Glycosphingolipids are important building blocks of the outer leaflet of the cell membrane. They are continuously recycled, involving fragmentation inside lysosomes by glycosidases. Inherited... Show moreGlycosphingolipids are important building blocks of the outer leaflet of the cell membrane. They are continuously recycled, involving fragmentation inside lysosomes by glycosidases. Inherited defects in degradation cause lysosomal glycosphingolipid storage disorders. The relatively common glycosphingolipidosis Gaucher disease is highlighted here to discuss new insights in the molecular basis and pathophysiology of glycosphingolipidoses reached by fundamental research increasingly using chemical biology tools. We discuss improvements in the detection of glycosphingolipid metabolites by mass spectrometry and review new developments in laboratory diagnosis and disease monitoring as well as therapeutic interventions. Show less
Wu, L.; Armstrong, Z.; Schröder, S.P.; Boer, C. de; Artola, M.; Aerts, J.M.F.G.; ... ; Davies, G.J. 2019
As the scope of modern genomics technologies increases, so does the need for informative chemical tools to study functional biology. Activity-based probes (ABPs) provide a powerful suite of... Show moreAs the scope of modern genomics technologies increases, so does the need for informative chemical tools to study functional biology. Activity-based probes (ABPs) provide a powerful suite of reagents to probe the biochemistry of living organisms. These probes, featuring a specificity motif, a reactive chemical group and a reporter tag, are opening-up large swathes of protein chemistry to investigation in vitro, as well as in cellular extracts, cells and living organisms in vivo. Glycoside hydrolases, by virtue of their prominent biological and applied roles, provide a broad canvas on which ABPs may illustrate their functions. Here we provide an overview of glycosidase ABP mechanisms, and review recent ABP work in the glycoside hydrolase field, encompassing their use in medical diagnosis, their application for generating chemical genetic disease models, their fine-tuning through conformational and reactivity insight, their use for high-throughput inhibitor discovery, and their deployment for enzyme discovery and dynamic characterization. Show less
