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...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 34(2018), 17 vom: 01. Mai, Seite 5106-5115 |
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| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| 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 |
| Zusammenfassung: | 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 |
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| Beschreibung: | Date Completed 14.03.2019 Date Revised 14.03.2019 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.8b00254 |