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Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici

The plant disease Phytophthora blight, caused by the oomycete pathogen Phytophthora capsici, is responsible for major economic losses in pepper production. Microtubules have been an attractive target for many antifungal agents as they are involved in key cellular events such as cell proliferation, s...

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Autores principales: Lee, Sang-Choon, Kim, Sang-Heon, Hoffmeister, Rachel A., Yoon, Moon-Young, Kim, Sung-Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600545/
https://www.ncbi.nlm.nih.gov/pubmed/31146360
http://dx.doi.org/10.3390/ijms20112641
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author Lee, Sang-Choon
Kim, Sang-Heon
Hoffmeister, Rachel A.
Yoon, Moon-Young
Kim, Sung-Kun
author_facet Lee, Sang-Choon
Kim, Sang-Heon
Hoffmeister, Rachel A.
Yoon, Moon-Young
Kim, Sung-Kun
author_sort Lee, Sang-Choon
collection PubMed
description The plant disease Phytophthora blight, caused by the oomycete pathogen Phytophthora capsici, is responsible for major economic losses in pepper production. Microtubules have been an attractive target for many antifungal agents as they are involved in key cellular events such as cell proliferation, signaling, and migration in eukaryotic cells. In order to design a novel biocompatible inhibitor, we screened and identified inhibitory peptides against alpha- and beta-tubulin of P. capsici using a phage display method. The identified peptides displayed a higher binding affinity (nanomolar range) and improved specificity toward P. capsici alpha- and beta-tubulin in comparison to Homo sapiens tubulin as evaluated by fluorometric analysis. One peptide demonstrated the high inhibitory effect on microtubule formation with a nanomolar range of IC(50) values, which were much lower than a well-known chemical inhibitor—benomyl (IC(50) = 500 µM). Based on these results, this peptide can be employed to further develop promising candidates for novel antifungal agents against Phytophthora blight.
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spelling pubmed-66005452019-07-16 Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici Lee, Sang-Choon Kim, Sang-Heon Hoffmeister, Rachel A. Yoon, Moon-Young Kim, Sung-Kun Int J Mol Sci Article The plant disease Phytophthora blight, caused by the oomycete pathogen Phytophthora capsici, is responsible for major economic losses in pepper production. Microtubules have been an attractive target for many antifungal agents as they are involved in key cellular events such as cell proliferation, signaling, and migration in eukaryotic cells. In order to design a novel biocompatible inhibitor, we screened and identified inhibitory peptides against alpha- and beta-tubulin of P. capsici using a phage display method. The identified peptides displayed a higher binding affinity (nanomolar range) and improved specificity toward P. capsici alpha- and beta-tubulin in comparison to Homo sapiens tubulin as evaluated by fluorometric analysis. One peptide demonstrated the high inhibitory effect on microtubule formation with a nanomolar range of IC(50) values, which were much lower than a well-known chemical inhibitor—benomyl (IC(50) = 500 µM). Based on these results, this peptide can be employed to further develop promising candidates for novel antifungal agents against Phytophthora blight. MDPI 2019-05-29 /pmc/articles/PMC6600545/ /pubmed/31146360 http://dx.doi.org/10.3390/ijms20112641 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Sang-Choon
Kim, Sang-Heon
Hoffmeister, Rachel A.
Yoon, Moon-Young
Kim, Sung-Kun
Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title_full Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title_fullStr Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title_full_unstemmed Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title_short Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora capsici
title_sort novel peptide-based inhibitors for microtubule polymerization in phytophthora capsici
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600545/
https://www.ncbi.nlm.nih.gov/pubmed/31146360
http://dx.doi.org/10.3390/ijms20112641
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