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001-es BibID:	BIBFORM124087
035-os BibID:	(WoS)001061261800001 (Scopus)85171309454
Első szerző:	Lázár László (vegyész)
Cím:	Strong Binding of C-Glycosylic1,2-Thiodisaccharides to Galectin-3 - Enthalpy-Driven Affinity Enhancement by Water-Mediated Hydrogen Bonds / László Lázár, Anastasia S. Tsagkarakou, George Stravodimos, George Kontopidis, Hakon Leffler, Ulf J. Nilsson, László Somsák, Demetres D. Leonidas
Dátum:	2023
ISSN:	0022-2623 1520-4804
Megjegyzések:	Galectin-3 is involved in multiple pathways of many diseases, including cancer, fibrosis, and diabetes, and it is a validated pharmaceutical target for the development of novel therapeutic agents to address unmet medical needs. Novel 1,2-thiodisaccharides with a C-glycosylic functionality were synthesized by the photoinitiated thiol-ene click reaction of O-peracylated 1-C-substituted glycals and 1-thio-glycopyranoses. Subsequent global deprotection yielded test compounds, which were studied for their binding to human galectin-3 by fluorescence polarization and isothermal titration calorimetry to show low micromolar Kd values. The best inhibitor displayed a Kd value of 8.0 ?M. An analysis of the thermodynamic binding parameters revealed that the binding Gibbs free energy (?G) of the new inhibitors was dominated by enthalpy (?H). The binding mode of the four most efficient 1,2-thiodisaccharides was also studied by X-ray crystallography that uncovered the unique role of water-mediated hydrogen bonds in conferring enthalpy-driven affinity enhancement for the new inhibitors. This 1,2-thiodisaccharide-type scaffold represents a new lead for galectin-3 inhibitor discovery and offers several possibilities for further development.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal of Medicinal Chemistry. - 66 : 17 (2023), p. 12420-12431. -
További szerzők:	Tsagkarakou, Anastasia S. Stravodimos, George A. Kontopidis, George Leffler, Hakon Nilsson, Ulf J. Somsák László (1954-) (vegyész) Leonidas, Demetres D.
Pályázati támogatás:	K109450 OTKA K146147 OTKA
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM099800
Első szerző:	Tsagkarakou, Anastasia S.
Cím:	Structure activity relationship of the binding of p-coumaroyl glucose to glycogen phosphorylase and its effect on hepatic cell metabolic pathways / Anastasia S. Tsagkarakoua, Styliani A. Chasapi, Symeon M. Koulas, Ioannis Tsialtas, Efthimios Kyriakis, Christina E. Drakou, Sándor Kun, László Somsák, Georgios A. Spyroulias, Anna-Maria G. Psarra, Demetres D. Leonidas
Dátum:	2021
ISSN:	2772-4174
Megjegyzések:	The binding of p-coumaroyl glucose to glycogen phosphorylase (GP; a pharmaceutical target for the development of antihyperglycaemic drugs) has been studied by kinetics, and X-ray crystallography while its effect to HepG2 cells metabolism has been assessed by NMR metabolomics. p-Coumaroyl glucose is a potent inhibitor of human liver GP with a Ki value of 213 ?? that binds at the active site of the enzyme. Comparative structural analysis with chemically similar GP inhibitors reveals the structural basis of its inhibitory potency. NMR metabolomics analysis revealed that HepG2 cells in the presence of p-coumaroyl glucose actively response to higher glucose uptake from their environment and a display an "insulin-sensitizing'' state. Furthermore, NMR metabolomics analysis indicates an enhancement of gluconeogenesis towards lipid metabolism and glycerol-derived components.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Glycogen phosphorylase Enzyme inhibition X-ray crystallography p-Coumaroyl glucose Glycogen metabolism NMR metabolomics
Megjelenés:	European Journal of Medicinal Chemistry Reports. - 3 (2021), p. 1-11. -
További szerzők:	Chasapi, Styliani A. Koulas, Symeon M. Tsialtas, Ioannis Kyriakis, Efthimios Drakou, Christina E. Kun Sándor (1984-) (vegyész) Somsák László (1954-) (vegyész) Spyroulias, Georgios A. Psarra, Anna-Maria G. Leonidas, Demetres D.
Pályázati támogatás:	FK132222 Egyéb GINOP-2.3.2-15-2016-00008 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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