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Tailor-made Janus Lectin with Dual Avidity Assembles Glycoconjugate Multilayers and Crosslinks Protocells
Abstract: We engineered the first chimeric, bispecific lectin, with two rationally oriented and distinct recognition surfaces. This lectin, coined Janus lectin in allusion to the two-faced roman god, is able to bind independently to both fucosylated and sialylated glycoconjugates. The multivalent presentation of binding sites on each face of the Janus lectin is very efficient, resulting in avidities in the low nanomolar range for both fucosylated and sialylated surfaces. Moreover, novel heterovalent, bifunctional glycoclusters were synthetized that match the topology of the Janus lectin. Based on these tools, we constructed organized and controlled supramolecular architectures by assembling Janus lectin and glycocompound layer-by-layer. Furthermore, the Janus lectin was employed as biomolecular linker to organize protocells made from giant unilamellar vesicles of different nature, to more complex prototissues. In summary, tailor-made Janus lectins open wide possibilities for creating biomimetic matrices or artificial tissues
A Shiga Toxin B-subunit-based Lectibody Boosts T Cell Cytotoxicity Towards Gb3-positive Cancer Cells
Abstract: Aberrant glycosylation plays a crucial role in tumour progression and invasiveness. Tumour-associated carbohydrate antigens (TACAs) represent a valuable set of targets for immunotherapeutic approaches. The poor immunogenicity of glycan structures, however, requires a more effective and well-directed way of targeting TACAs on the surface of cancer cells than antibodies. The glycosphingolipid globotriaosylceramide (Gb3) is a well-established TACA present in a multitude of cancer types. Its overexpression has been linked to metastasis, invasiveness, and multidrug resistance. In the present study, we propose to use a dimeric fragment of the Shiga toxin B-subunit (StxB) to selectively t...
Glycobiology Protocols
Glycobiology involves studies of complex carbohydrates and posttrans- tional modifications of proteins, and has become an important interdiscip- nary field encompassing chemistry, biochemistry, biology, physiology, and pathology. Although initial research was directed toward elucidation of the different carbohydrate structures and the enzymes synthesizing them, the field has now moved toward identifying the functions of carbohydrates. The pro- cols described in Glycobiology Protocols form a solid basis for investigations of glycan functions in health and disease. The cloning of many of the genes participating in glycosylation processes has helped to enhance our knowledge of how glycosylation...
Synthesis and Biological Applications of Glycoconjugates
The interactions between carbohydrates and proteins have been extensively explored in a wide range of physiological and pathological processes over several decades. The recent emergence of glycomics has strengthened this interest and notably contributed t
Glycoscience
As a reflection of the quantum leap that has been made in the study of glycostructures, the first edition of this book has been completely revised and updated. The editors give up-to-date information on glycostructures, their chemistry and chemical biology in the form of a completely comprehensive survey. Glycostructures play highly diverse and crucial roles in a myriad of organisms and important systems in biology, physiology, medicine, bioengineering and technology. Only in recent years have the tools been developed to partly understand the highly complex functions and the chemistry behind them. While many facts remain undiscovered, this MRW has been contributed to by a large number of the world’s leading researchers in the field.
Carbohydrate Recognition
This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.
