Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin

Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for...

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Main Authors: Kragh-Hansen, U., Chuang, Victor, Otagiri, M.
Format: Journal Article
Published: Pharmaceutical Society of Japan 2002
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/12581
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author Kragh-Hansen, U.
Chuang, Victor
Otagiri, M.
author_facet Kragh-Hansen, U.
Chuang, Victor
Otagiri, M.
author_sort Kragh-Hansen, U.
building Curtin Institutional Repository
collection Online Access
description Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for the possible construction of therapeutic agents with altered HSA-binding properties. A tabulation of high-affinity binding sites for both endogenous and exogenous compounds has been made; it could be useful for the above-mentioned purpose, but it could also be of value when trying to predict potential drug interactions at the protein-binding level. Drug displacement is not always a complication to therapy; it can be used to increase the biological effect of a drug. However, due to rebinding at other sites, the increase in the free concentration of a displaced ligand can be less than expected.Drugs and drug metabolites can also interact covalently with HSA; thiol-containing drugs often bind to the single free cysteine residue of HSA, and glucuronidated drugs react irreversibly with other residues of the protein. Reversible binding of ligands is often stereospecific, and therefore immobilized HSA can be used to separate drug isomers. Albumin-containing dialysates are useful for extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. HSA has different types of hydrolytic activities, which also can be stereospecific. The esterase-like property seems especially useful in converting prodrugs to active drugs in plasma.
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spelling curtin-20.500.11937-125812017-01-30T11:31:33Z Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin Kragh-Hansen, U. Chuang, Victor Otagiri, M. mutual displacement covalent binding high-affinity binding site extracorporeal clearance immobilized albumin enzymatic property Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for the possible construction of therapeutic agents with altered HSA-binding properties. A tabulation of high-affinity binding sites for both endogenous and exogenous compounds has been made; it could be useful for the above-mentioned purpose, but it could also be of value when trying to predict potential drug interactions at the protein-binding level. Drug displacement is not always a complication to therapy; it can be used to increase the biological effect of a drug. However, due to rebinding at other sites, the increase in the free concentration of a displaced ligand can be less than expected.Drugs and drug metabolites can also interact covalently with HSA; thiol-containing drugs often bind to the single free cysteine residue of HSA, and glucuronidated drugs react irreversibly with other residues of the protein. Reversible binding of ligands is often stereospecific, and therefore immobilized HSA can be used to separate drug isomers. Albumin-containing dialysates are useful for extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. HSA has different types of hydrolytic activities, which also can be stereospecific. The esterase-like property seems especially useful in converting prodrugs to active drugs in plasma. 2002 Journal Article http://hdl.handle.net/20.500.11937/12581 Pharmaceutical Society of Japan restricted
spellingShingle mutual displacement
covalent binding
high-affinity binding site
extracorporeal clearance
immobilized albumin
enzymatic property
Kragh-Hansen, U.
Chuang, Victor
Otagiri, M.
Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title_full Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title_fullStr Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title_full_unstemmed Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title_short Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin
title_sort practical aspects of the ligand-binding and enzymatic properties of human serum albumin
topic mutual displacement
covalent binding
high-affinity binding site
extracorporeal clearance
immobilized albumin
enzymatic property
url http://hdl.handle.net/20.500.11937/12581