Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?
Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N–glycan chains of alpha-1 acid glycoprotein change in response...
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2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Robert Kerep Tino Šeba Valentina Borko Tin Weitner Toma Keser Gordan Lauc Mario Gabričević |
| author_facet | Robert Kerep Tino Šeba Valentina Borko Tin Weitner Toma Keser Gordan Lauc Mario Gabričević |
| author_sort | Robert Kerep |
| collection | DOAJ |
| description | Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N–glycan chains of alpha-1 acid glycoprotein change in response to certain health conditions and may have a major impact on drug binding to alpha-1 acid glycoprotein. The interaction between native or desialylated alpha-1 acid glycoprotein and four representative drugs—clindamycin, diltiazem, lidocaine, and warfarin—was quantitatively evaluated using isothermal titration calorimetry. The calorimetry assay used here is a convenient and widely used approach to directly measure the amount of heat released or absorbed during the association processes of biomolecules in solution and to quantitatively estimate the thermodynamics of the interaction. The results showed that the binding of drugs with alpha-1 acid glycoprotein were enthalpy-driven exothermic interactions, and the binding affinity was in the range of 10<sup>−5</sup>–10<sup>−6</sup> M. Desialylated alpha-1 acid glycoprotein showed significantly different binding with diltiazem, lidocaine, and warfarin compared with native alpha-1 acid glycoprotein, whereas clindamycin showed no significant difference. Therefore, a different degree of sialylation may result in different binding affinities, and the clinical significance of changes in sialylation or glycosylation of alpha-1 acid glycoprotein in general should not be neglected. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:34Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6df24b0bcfd94d498a5c87da6962ed412023-11-18T01:36:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410847210.3390/ijms24108472Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?Robert Kerep0Tino Šeba1Valentina Borko2Tin Weitner3Toma Keser4Gordan Lauc5Mario Gabričević6Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaHuman serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N–glycan chains of alpha-1 acid glycoprotein change in response to certain health conditions and may have a major impact on drug binding to alpha-1 acid glycoprotein. The interaction between native or desialylated alpha-1 acid glycoprotein and four representative drugs—clindamycin, diltiazem, lidocaine, and warfarin—was quantitatively evaluated using isothermal titration calorimetry. The calorimetry assay used here is a convenient and widely used approach to directly measure the amount of heat released or absorbed during the association processes of biomolecules in solution and to quantitatively estimate the thermodynamics of the interaction. The results showed that the binding of drugs with alpha-1 acid glycoprotein were enthalpy-driven exothermic interactions, and the binding affinity was in the range of 10<sup>−5</sup>–10<sup>−6</sup> M. Desialylated alpha-1 acid glycoprotein showed significantly different binding with diltiazem, lidocaine, and warfarin compared with native alpha-1 acid glycoprotein, whereas clindamycin showed no significant difference. Therefore, a different degree of sialylation may result in different binding affinities, and the clinical significance of changes in sialylation or glycosylation of alpha-1 acid glycoprotein in general should not be neglected.https://www.mdpi.com/1422-0067/24/10/8472alpha-1 acid glycoproteindrugsplasma protein bindingsialic acidbinding affinityisothermal titration calorimetry |
| spellingShingle | Robert Kerep Tino Šeba Valentina Borko Tin Weitner Toma Keser Gordan Lauc Mario Gabričević Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? International Journal of Molecular Sciences alpha-1 acid glycoprotein drugs plasma protein binding sialic acid binding affinity isothermal titration calorimetry |
| title | Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? |
| title_full | Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? |
| title_fullStr | Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? |
| title_full_unstemmed | Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? |
| title_short | Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics? |
| title_sort | potential clinically relevant effects of sialylation on human serum aag drug interactions assessed by isothermal titration calorimetry insight into pharmacoglycomics |
| topic | alpha-1 acid glycoprotein drugs plasma protein binding sialic acid binding affinity isothermal titration calorimetry |
| url | https://www.mdpi.com/1422-0067/24/10/8472 |
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