國家衛生研究院 NHRI:Item 3990099045/4019
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4019


    Title: Small-molecule peptides inhibit Z alpha1-antitrypsin polymerization
    Other Titles: Small-molecule peptides inhibit Z alpha(1)-antitrypsin olymerization
    Authors: Chang, YP;Mahadeva, R;Chang, WSW;Lin, SC;Chu, YH
    Contributors: National Institute of Cancer Research
    Abstract: The Z variant of α<sub>1</sub>-antitrypsin (AT) polymerizes within the liver and gives rise to liver cirrhosis and the associated plasma deficiency leads to emphysema. In this work, a combinatorial approach based on the inhibitory mechanism of α<sub>1</sub>-AT was developed to arrest its pathogenic polymerization. One peptide, Ac-TTAI-NH<sub>2</sub>, emerged as the most tight-binding ligand for Z α<sub>1</sub>-AT. Characterization of this tetrapeptide by gel electrophoresis and biosensor analysis revealed its markedly improved binding specificity and affinity compared with all previously reported peptide inhibitors. In addition, the peptide is not cytotoxic to lung cell lines. A model of the peptide-protein complex suggests that the peptide interacts with nearby residues by hydrogen bonds, hydrophobic interactions, and cavity-filling stabilization. The combinatorially selected peptide not only effectively blocks the polymerization but also promotes dissociation of the oligomerized α<sub>1</sub>-AT. These results are a significant step towards the potential treatment of Z α<sub>1</sub>-AT related diseases.
    Date: 2009-08
    Relation: Journal of Cellular and Molecular Medicine. 2009 Aug;13(8B):2304-2316.
    Link to: http://dx.doi.org/10.1111/j.1582-4934.2008.00608.x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1582-1838&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000272190800062
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=72949086203
    Appears in Collections:[Wun-Shaing Wayne Chang] Periodical Articles

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