Towards broad spectrum activity-based glycosidase probes: synthesis and evaluation of deoxygenated cyclophellitol aziridines.

Towards broad spectrum activity - based glycosidase probes : synthesis and evaluation of deoxygenated cyclophellitol aziridines

1,6-Cyclophellitol Cyclosulfates: A New Class of Irreversible Glycosidase Inhibitor

The essential biological roles played by glycosidases, coupled to the diverse therapeutic benefits of pharmacologically targeting these enzymes, provide considerable motivation for the development of new inhibitor classes. Cyclophellitol epoxides and aziridines are recently established covalent glycosidase inactivators. Inspired by the application of cyclic sulfates as electrophilic equivalents...

Correction to “Detection of Active Mammalian GH31 α-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes”

The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. α-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing i...

In vitro and in vivo comparative and competitive activity-based protein profiling of GH29 α-l-fucosidases.

GH29 α-l-fucosidases catalyze the hydrolysis of α-l-fucosidic linkages. Deficiency in human lysosomal α-l-fucosidase (FUCA1) leads to the recessively inherited disorder, fucosidosis. Herein we describe the development of fucopyranose-configured cyclophellitol aziridines as activity-based probes (ABPs) for selective in vitro and in vivo labeling of GH29 α-l-fucosidases from bacteria, mice and ma...

Stereocontrolled synthesis of beta-amino alcohols from lithiated aziridines and boronic esters.

From natural products to ligands for asymmetric catalysis, the b-amino alcohol motif is ubiquitous. The importance of this motif to such a broad spectrum of chemistry has prompted the development of a range of methodologies for its synthesis which include Sharpless aminohydroxylation as well as the addition of nucleophiles to aminocarbonyls, imines, epoxides, and aziridines. We considered a con...