Dr. Anne Imberty
CERMAV, CNRS and Université Grenoble Alpes, France
Lectins and lectomes: from therapeutical targets to synthetic glycobiology
A large number of pathogenic microorganisms display receptors for specific recognition and adhesion to the glycoconjugates present on human tissues. In addition to membrane-bound adhesins, soluble lectins are involved in lung infections caused by the bacteria Pseudomonas aeruginosa and Burkholderia cepacia and by the fungus Aspergillus fumigatus that are responsible for hospital-acquired diseases. The multivalency of lectin is proposed to play a role in their strong avidity for glycosylated cell surfaces, their specific binding to some cell types, and also in their ability to affect membrane dynamics by clustering glycosphingolipids, resulting in some cases in internalization of intracellular pathogens.
Accumulated knowledge about the structures of the lectins and the interactions with host glycoconjugates has led to the design of powerful glyco-derived inhibitors that can serve as antimicrobial therapeutic agents, as a complement to or an alternative to antibiotic therapy. Several strategies are developed: glycoderivatives with increased affinity, glycomimetics with no carbohydrate moiety or multivalent compounds that make use of the receptor architecture.
On the other hand, bacterial lectins are superb tools for idenfying, purifying and labelling glycoconjugates and can be used for vectorisation or as glue for creating artificial tissue. Synthetic glycobiology offers innovative methods for building super-lectins as novel architectures.
- S. Kuhaudomlar, E. Siebs, E. Shanina, J. Topin, I. Joachim, P. da Silva Figueiredo Celestino Gomes, A. Varrot, D. Rognan, C. Rademacher, A. Imberty & A. Titz (2021) Non-carbohydrate glycomimetics as inhibitors of calcium(II)-binding lectins. Angew Chem 60, 2-13
- S. Notova, F. Bonnardel, F. Rosato, L Siukstaite, J. Schwaiger, N. Bovin, A. Varrot, W. Römer, F. Lisacek & A. Imberty (2022) The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3. Commun Biol 5, 954
- S. Notova & A. Imberty (2023) Tuning specificity and topology of lectins through synthetic biology. Curr Opin Chem Biol 102, 102275