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001-es BibID:	BIBFORM101136
035-os BibID:	(cikkazonosító)2494 (scopus)85125044439 (wos)000768200600001
Első szerző:	Hadháziné Raics Mária (vegyész)
Cím:	Investigation of the Molecular Details of the Interactions of Selenoglycosides and Human Galectin-3 / Mária Raics, Álex Kálmán Balogh, Chandan Kishor, István Timári, Francisco J. Medrano, Antonio Romero, Rob Marc Go, Helen Blanchard, László Szilágyi, Katalin E. Kövér, Krisztina Fehér
Dátum:	2022
ISSN:	1661-6596 1422-0067
Megjegyzések:	Human galectin-3 (hGal-3) is involved in a variety of biological processes and is implicated in wide range of diseases. As a result, targeting hGal-3 for clinical applications has become an intense area of research. As a step towards the development of novel hGal-3 inhibitors, we describe a study of the binding of two Se-containing hGal-3 inhibitors, specifically that of di(?-Dgalactopyranosyl)selenide (SeDG), in which two galactose rings are linked by one Se atom and a di(?-D-galactopyranosyl)diselenide (DSeDG) analogue with a diseleno bond between the two sugar units. The binding affinities of these derivatives to hGal-3 were determined by 15N-1H HSQC NMR spectroscopy and fluorescence anisotropy titrations in solution, indicating a slight decrease in the strength of interaction for SeDG compared to thiodigalactoside (TDG), a well-known inhibitor of hGal-3, while DSeDG displayed a much weaker interaction strength. NMR and FA measurements showed that both seleno derivatives bind to the canonical S face site of hGal-3 and stack against the conserved W181 residue also confirmed by X-ray crystallography, revealing canonical properties of the interaction. The interaction with DSeDG revealed two distinct binding modes in the crystal structure which are in fast exchange on the NMR time scale in solution, explaining a weaker interaction with hGal-3 than SeDG. Using molecular dynamics simulations, we have found that energetic contributions to the binding enthalpies mainly differ in the electrostatic interactions and in polar solvation terms and are responsible for weaker binding of DSeDG compared to SeDG. Selenium-containing carbohydrate inhibitors of hGal-3 showing canonical binding modes offer the potential of becoming novel hydrolytically stable scaffolds for a new class of hGal-3 inhibitors.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk lectin galectin-3 selenoglycosides NMR spectroscopy fluorescence anisotropy X-ray crystallography molecular dynamics
Megjelenés:	International Journal of Molecular Sciences. - 23 : 5 (2022), p. 1-17. -
További szerzők:	Balogh Álex Kálmán (1994-) (vegyész) Kishor, Chandan Timári István (1989-) (vegyész) Medrano, Francisco J. Romero, Antonio Go, Rob Marc Blanchard, Helen Szilágyi László (1941-) (vegyész) Kövér Katalin, E. (1956-2023) (vegyész) Fehér Krisztina (1974-) (vegyész)
Pályázati támogatás:	NN 128368 OTKA PD 135034 OTKA GINOP-2.3.3-15-2016-00004 GINOP GINOP-2.3.2-15-2016-00008 GINOP BO/00372/20/7 Egyéb ÚNKP-21-5-DE-471 Egyéb BO/004333/18/7 Egyéb ÚNKP-21-4-DE-165 Egyéb
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