Structural Basis of Drug Recognition by Human Serum Albumin.
Human serum albumin
allosteric modulation of drug
binding
competitive modulation of drug binding
drug carrier
drug recognition
structural basis
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
11
2018
revised:
12
02
2019
accepted:
06
03
2019
pubmed:
22
3
2019
medline:
26
9
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs. In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed. As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.
Sections du résumé
BACKGROUND
BACKGROUND
Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.
OBJECTIVE
OBJECTIVE
In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.
CONCLUSION
CONCLUSIONS
As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.
Identifiants
pubmed: 30894098
pii: CMC-EPUB-97445
doi: 10.2174/0929867326666190320105316
doi:
Substances chimiques
Ligands
0
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4907-4931Informations de copyright
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