Bifunctionality of Iminodiacetic Acid-Modified Lysozyme on Inhibiting Zn2+-Mediated Amyloid β-Protein Aggregation

Aggregation of amyloid β-proteins (Aβ) mediated by metal ions such as Zn2+ has been suggested to be implicated in the progression of Alzheimer's disease (AD). Hence, development of bifunctional agents capable of inhibiting Aβ aggregation and modulating metal-Aβ species is an effective strategy...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 34(2018), 17 vom: 01. Mai, Seite 5106-5115
1. Verfasser: Li, Xi (VerfasserIn)
Weitere Verfasser: Xie, Baolong, Dong, Xiaoyan, Sun, Yan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Amyloid beta-Peptides Imino Acids Muramidase EC 3.2.1.17 Zinc J41CSQ7QDS iminodiacetic acid XQM2L81M8Z
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520 |a Aggregation of amyloid β-proteins (Aβ) mediated by metal ions such as Zn2+ has been suggested to be implicated in the progression of Alzheimer's disease (AD). Hence, development of bifunctional agents capable of inhibiting Aβ aggregation and modulating metal-Aβ species is an effective strategy for the treatment of AD. In this work, we modified iminodiacetic acid (IDA) onto human lysozyme (hLys) surface to create an inhibitor of Zn2+-mediated Aβ aggregation and cytotoxicity. The IDA-modified hLys (IDA-hLys) retained the stability and biocompatibility of native hLys. Extensive biophysical and biological analyses indicated that IDA-hLys significantly attenuated Zn2+-mediated Aβ aggregation and cytotoxicity due to its strong binding affinity for Zn2+, whereas native hLys showed little effect. Stopped-flow fluorescence spectroscopy showed that IDA-hLys could protect Aβ from Zn2+-induced aggregation and rapidly depolymerize Zn2+-Aβ aggregates. The research indicates that IDA-hLys is a bifunctional agent capable of inhibiting Aβ fibrillization and modulating Zn2+-mediated Aβ aggregation and cytotoxicity as a strong Zn2+ chelator 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a Amyloid beta-Peptides  |2 NLM 
650 7 |a Imino Acids  |2 NLM 
650 7 |a Muramidase  |2 NLM 
650 7 |a EC 3.2.1.17  |2 NLM 
650 7 |a Zinc  |2 NLM 
650 7 |a J41CSQ7QDS  |2 NLM 
650 7 |a iminodiacetic acid  |2 NLM 
650 7 |a XQM2L81M8Z  |2 NLM 
700 1 |a Xie, Baolong  |e verfasserin  |4 aut 
700 1 |a Dong, Xiaoyan  |e verfasserin  |4 aut 
700 1 |a Sun, Yan  |e verfasserin  |4 aut 
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