Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin

Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to their anti-inflammatory and anti-oxidant properties. They mainly bind to albumin in plasma. These findings influence their body d...

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Main Authors: Sato, H., Chuang, Victor, Yamasaki, K., Yamaotsu, N., Watanabe, H., Nagumo, K., Anraku, M., Kadowaki, D., Ishima, Y., Hirono, S., Otagiri, M., Maruyama, T.
Format: Journal Article
Published: Public Library of Science 2014
Online Access:http://hdl.handle.net/20.500.11937/17812
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author Sato, H.
Chuang, Victor
Yamasaki, K.
Yamaotsu, N.
Watanabe, H.
Nagumo, K.
Anraku, M.
Kadowaki, D.
Ishima, Y.
Hirono, S.
Otagiri, M.
Maruyama, T.
author_facet Sato, H.
Chuang, Victor
Yamasaki, K.
Yamaotsu, N.
Watanabe, H.
Nagumo, K.
Anraku, M.
Kadowaki, D.
Ishima, Y.
Hirono, S.
Otagiri, M.
Maruyama, T.
author_sort Sato, H.
building Curtin Institutional Repository
collection Online Access
description Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to their anti-inflammatory and anti-oxidant properties. They mainly bind to albumin in plasma. These findings influence their body disposition and biological activities. Spectroscopic analysis using site specific probes on human serum albumin (HSA) clearly indicated that curcumin (Cur), demethylcurcumin (Dmc) and bisdemethoxycurcumin (Bdmc) bind to both Site I (sub-site Ia and Ib) and Site II on HSA. At pH 7.4, the binding constants for Site I were relatively comparable between curcuminoids, while the binding constants for Site II at pH 7.4 were increased in order Cur , Dmc , Bdmc. Binding experiments using HSA mutants showed that Trp214 and Arg218 at Site I, and Tyr411 and Arg410 at Site II are involved in the binding of curcuminoids. The molecular docking of all curcuminoids to the Site I pocket showed that curcuminoids stacked with Phe211 and Trp214, and interacted with hydrophobic and aromatic amino acid residues. In contrast, each curcuminoid interacted with Site II in a different manner depending whether a methoxy group was present or absent. A detailed analysis of curcuminoids-albumin interactions would provide valuable information in terms of understanding the pharmacokinetics and the biological activities of this class of compounds.
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spelling curtin-20.500.11937-178122017-09-13T15:43:29Z Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin Sato, H. Chuang, Victor Yamasaki, K. Yamaotsu, N. Watanabe, H. Nagumo, K. Anraku, M. Kadowaki, D. Ishima, Y. Hirono, S. Otagiri, M. Maruyama, T. Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to their anti-inflammatory and anti-oxidant properties. They mainly bind to albumin in plasma. These findings influence their body disposition and biological activities. Spectroscopic analysis using site specific probes on human serum albumin (HSA) clearly indicated that curcumin (Cur), demethylcurcumin (Dmc) and bisdemethoxycurcumin (Bdmc) bind to both Site I (sub-site Ia and Ib) and Site II on HSA. At pH 7.4, the binding constants for Site I were relatively comparable between curcuminoids, while the binding constants for Site II at pH 7.4 were increased in order Cur , Dmc , Bdmc. Binding experiments using HSA mutants showed that Trp214 and Arg218 at Site I, and Tyr411 and Arg410 at Site II are involved in the binding of curcuminoids. The molecular docking of all curcuminoids to the Site I pocket showed that curcuminoids stacked with Phe211 and Trp214, and interacted with hydrophobic and aromatic amino acid residues. In contrast, each curcuminoid interacted with Site II in a different manner depending whether a methoxy group was present or absent. A detailed analysis of curcuminoids-albumin interactions would provide valuable information in terms of understanding the pharmacokinetics and the biological activities of this class of compounds. 2014 Journal Article http://hdl.handle.net/20.500.11937/17812 10.1371/journal.pone.0087919 Public Library of Science fulltext
spellingShingle Sato, H.
Chuang, Victor
Yamasaki, K.
Yamaotsu, N.
Watanabe, H.
Nagumo, K.
Anraku, M.
Kadowaki, D.
Ishima, Y.
Hirono, S.
Otagiri, M.
Maruyama, T.
Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title_full Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title_fullStr Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title_full_unstemmed Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title_short Differential Effects of Methoxy Group on the Interaction of Curcuminoids with Two Major Ligand Binding Sites of Human Serum Albumin
title_sort differential effects of methoxy group on the interaction of curcuminoids with two major ligand binding sites of human serum albumin
url http://hdl.handle.net/20.500.11937/17812