Search

Your search keyword '"Pukin, Aliaksei"' showing total 27 results
Start Over Author "Pukin, Aliaksei" Database OAIster
27 results on '"Pukin, Aliaksei"'

1. Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate-based cholera toxin inhibitors

Author

Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, Pieters, Roland J, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, and Pieters, Roland J

Abstract

Developing tools for the study of protein carbohydrate interactions is an important goal in glycobiology. Cholera toxin inhibition is an interesting target in this context, as its inhibition may help to fight against cholera. For the study of novel ligands an affinity capillary electrophoresis (ACE) method was optimized and applied. The method uses unlabeled cholera toxin B-subunit (CTB) and unlabeled carbohydrate ligands based on ganglioside GM1-oligosaccharides (GM1os). In an optimized method at pH 4, adsorption of the protein to the capillary walls was prevented by a polybrene-dextran sulfate-polybrene coating. Different concentrations of the ligands were added to the BGE. CTB binding was observed by a mobility shift that could be used for dissociation constant (Kd ) determination. The Kd values of two GM1 derivatives differed by close to an order of magnitude (600 ± 20 nM and 90 ± 50 nM) which was in good agreement with the differences in their reported nanomolar IC50 values of an ELISA-type assay. Moreover, the selectivity of GM1os towards CTB was demonstrated using Influenza hemagglutinin (H5) as a binding competitor. The developed method can be an important platform for preclinical development of drugs targeting pathogen-induced secretory diarrhea.

Published
2018

2. Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate-based cholera toxin inhibitors

Author

Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, Pieters, Roland J, Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, and Pieters, Roland J

Published
2018

3. Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate-based cholera toxin inhibitors

Author

Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, Pieters, Roland J, Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, and Pieters, Roland J

Published
2018

4. Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate-based cholera toxin inhibitors

Author

Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, Pieters, Roland J, Afd Chemical Biology and Drug Discovery, Sub Algemeen Scheikunde, Chemical Biology and Drug Discovery, Aizpurua-Olaizola, Oier, Sastre Torano, Javier, Pukin, Aliaksei, Fu, Ou, Boons, Geert Jan, de Jong, Gerhardus J, and Pieters, Roland J

Published
2018

5. Functional characterization of cholera toxin inhibitors using human intestinal organoids

Author

Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., Pieters, Roland J., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., and Pieters, Roland J.

Abstract

Preclinical drug testing in primary human cell models that recapitulate disease can significantly reduce animal experimentation and time-to-the-clinic. We used intestinal organoids to quantitatively study the potency of multivalent cholera toxin inhibitors. The method enabled the determination of IC50 values over a wide range of potencies (15 pM to 9 mM). The results indicate for the first time that an organoid-based swelling assay is a useful preclinical method to evaluate inhibitor potencies of drugs that target pathogen-derived toxins.

Published
2016

8. Functional characterization of cholera toxin inhibitors using human intestinal organoids

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., and Pieters, Roland J.

Published
2016

10. Functional characterization of cholera toxin inhibitors using human intestinal organoids

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., and Pieters, Roland J.

Published
2016

11. Functional characterization of cholera toxin inhibitors using human intestinal organoids

Author

Beekman, Longziekten onderzoek 2, Child Health, UMC Utrecht, Regenerative Medicine and Stem Cells, Infection & Immunity, Zomer-van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., Pieters, Roland J., Beekman, Longziekten onderzoek 2, Child Health, UMC Utrecht, Regenerative Medicine and Stem Cells, Infection & Immunity, Zomer-van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., and Pieters, Roland J.

Published
2016

12. Functional characterization of cholera toxin inhibitors using human intestinal organoids

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Zomer-Van Ommen, Domenique D., Pukin, Aliaksei V., Fu, Ou, Quarles Van Ufford, Linda H C, Janssens, Hettie M., Beekman, Jeffrey M., and Pieters, Roland J.

Published
2016

13. Tetra- versus Pentavalent Inhibitors of Cholera Toxin

Author

Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., Pieters, Roland J., Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., and Pieters, Roland J.

Abstract

The five B-subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to the intestinal cell surface so the entire AB5 toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such simultaneous binding arising from the toxins multivalency is believed to enhance its affinity. Thus, blocking the initial attachment of the toxin to the cell surface using inhibitors with GM1 subunits has the potential to stop the disease. Previously we showed that tetravalent GM1 molecules were sub-nanomolar inhibitors of CTB5. In this study, we synthesized a pentavalent version and compared the binding and potency of penta- and tetravalent cholera toxin inhibitors, based on the same scaffold, for the first time. The pentavalent geometry did not yield major benefits over the tetravalent species, but it was still a strong inhibitor, and no major steric clashes occurred when binding the toxin. Thus, systems which can adopt more geometries, such as those described here, can be equally potent, and this may possibly be due to their ability to form higher-order structures or simply due to more statistical options for binding. Carbohydrates combating cholera! Simultaneous binding of the five B-subunits of the cholera toxin (CTB5) enhances its affinity and facilitates its cellular entry. Thus, blocking the toxins initial attachment to the cell surface could stop the disease. The binding pattern and potency of tetra- and pentavalent CTB5 inhibitors based on the same GM1 ganglioside scaffold are compared for the first time.

Published
2015

14. Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin

Author

Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., Pieters, Roland J., Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., and Pieters, Roland J.

Abstract

The bacterial adhesion lectin LecA is an attractive target for interference with the infectivity of its producer P.aeruginosa. Divalent ligands with two terminal galactoside moieties connected by an alternating glucose-triazole spacer were previously shown to be very potent inhibitors. In this study, we chose to prepare a series of derivatives with various new substituents in the spacer in hopes of further enhancing the LecA inhibitory potency of the molecules. Based on the binding mode, modifications were made to the spacer to enable additional spacer-protein interactions. The introduction of positively charged, negatively charged, and also lipophilic functional groups was successful. The compounds were good LecA ligands, but no improved binding was seen, even though altered thermodynamic parameters were observed by isothermal titration calorimetry (ITC). Linkers for lectin ligands! The P.aeruginosa lectin and virulence factor LecA can be efficiently blocked by divalent galactoside ligands containing a rigid spacer. Further functionalization of the spacer was explored in order to foster spacer-protein interactions. Positively and negatively charged groups as well as lipophilic groups were used for this purpose.

Published
2015

15. Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA

Author

Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, Pieters, Roland J, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, and Pieters, Roland J

Abstract

A new divalent highly potent inhibitor of the Pseudomonas aeruginosa lectin and virulence factor LecA was prepared. It contains two thiourea linkages which were found to be in the Z,Z isomeric form. This brings the spacer into an elongated conformation required to bridge the two binding sites, which results in the chelating binding mode responsible for the high potency.

Published
2015

16. Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Author

Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., Reymond, Jean Louis, Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., and Reymond, Jean Louis

Published
2015

17. Tetra- versus Pentavalent Inhibitors of Cholera Toxin

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., and Pieters, Roland J.

Published
2015

18. Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA

Author

Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, Pieters, Roland J, Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, and Pieters, Roland J

Published
2015

19. Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin

Author

Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., Pieters, Roland J., Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., and Pieters, Roland J.

Published
2015

20. Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Author

Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., Reymond, Jean Louis, Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., and Reymond, Jean Louis

Published
2015

21. Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin

Author

Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., Pieters, Roland J., Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., and Pieters, Roland J.

Published
2015

22. Tetra- versus Pentavalent Inhibitors of Cholera Toxin

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., and Pieters, Roland J.

Published
2015

23. Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA

Author

Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, Pieters, Roland J, Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, and Pieters, Roland J

Published
2015

24. Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA

Author

Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, Pieters, Roland J, Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pukin, Aliaksei V, Brouwer, Arwin J, Koomen, Leonie, Quarles van Ufford, H C, Kemmink, Johan, de Mol, Nico J, and Pieters, Roland J

Published
2015

25. Functionalization of a Rigid Divalent Ligand for LecA, a Bacterial Adhesion Lectin

Author

Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., Pieters, Roland J., Sub Medicinal Chemistry & Chemical biol., Chemical Biology, Medicinal Chemistry and Chemical Biology, Fu, Ou, Pukin, Aliaksei V., Quarlesvanufford, H. C., Kemmink, Johan, DeMol, Nico J., and Pieters, Roland J.

Published
2015

26. Tetra- versus Pentavalent Inhibitors of Cholera Toxin

Author

Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., Pieters, Roland J., Medicinal Chemistry and Chemical Biology, Sub Medicinal Chemistry & Chemical biol., Sub Physical and Colloid Chemistry, Faculty of Veterinary Medicine Research Groups, Fu, Ou, Pukin, Aliaksei V., Quarles Van Ufford, Linda, Branson, Thomas R., Thies-Weesie, Dominique M E, Turnbull, W. Bruce, Visser, Gerben M., and Pieters, Roland J.

Published
2015

27. Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA

Author

Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., Reymond, Jean Louis, Physical and Colloid Chemistry, Sub Medicinal Chemistry & Chemical biol., LS Infectiebiologie (Bacteriologie), Sub Physical and Colloid Chemistry, UIPS - Utrecht Institute for Pharmaceutical Sciences, Visini, Ricardo, Jin, Xian, Bergmann, Myriam, Michaud, Gaelle, Pertici, Francesca, Fu, Ou, Pukin, Aliaksei, Branson, Thomas R., Thies-Weesie, Dominique M E, Kemmink, Johan, Gillon, Emilie, Imberty, Anne, Stocker, Achim, Darbre, Tamis, Pieters, Roland J., and Reymond, Jean Louis

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results