Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?
alpha-1 acid glycoprotein
binding affinity
drugs
isothermal titration calorimetry
plasma protein binding
sialic acid
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 May 2023
09 May 2023
Historique:
received:
27
02
2023
revised:
18
04
2023
accepted:
25
04
2023
medline:
29
5
2023
pubmed:
27
5
2023
entrez:
27
5
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 37239819
pii: ijms24108472
doi: 10.3390/ijms24108472
pmc: PMC10218007
pii:
doi:
Substances chimiques
Warfarin
5Q7ZVV76EI
Clindamycin
3U02EL437C
Diltiazem
EE92BBP03H
Orosomucoid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Croatian Science Foundation
ID : IP-2016-06-3672, UIP-2017-05-9537
Organisme : European Structural and Investment Fund
ID : KK.01.1.1.07.0055
Organisme : European Regional Development Fund
ID : KK.01.1.1.02.0021, KK.01.1.1.01.0010
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