Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome

Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(...

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Autores principales: Ma, Yuheng, Xu, Bo, Fang, Yuan, Yang, Zhenjun, Cui, Jingrong, Zhang, Liangren, Zhang, Lihe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264673/
https://www.ncbi.nlm.nih.gov/pubmed/21894088
http://dx.doi.org/10.3390/molecules16097551
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author Ma, Yuheng
Xu, Bo
Fang, Yuan
Yang, Zhenjun
Cui, Jingrong
Zhang, Liangren
Zhang, Lihe
author_facet Ma, Yuheng
Xu, Bo
Fang, Yuan
Yang, Zhenjun
Cui, Jingrong
Zhang, Liangren
Zhang, Lihe
author_sort Ma, Yuheng
collection PubMed
description Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed.
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spelling pubmed-62646732018-12-10 Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome Ma, Yuheng Xu, Bo Fang, Yuan Yang, Zhenjun Cui, Jingrong Zhang, Liangren Zhang, Lihe Molecules Article Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed. MDPI 2011-09-05 /pmc/articles/PMC6264673/ /pubmed/21894088 http://dx.doi.org/10.3390/molecules16097551 Text en © 2011 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Ma, Yuheng
Xu, Bo
Fang, Yuan
Yang, Zhenjun
Cui, Jingrong
Zhang, Liangren
Zhang, Lihe
Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title_full Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title_fullStr Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title_full_unstemmed Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title_short Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
title_sort synthesis and sar study of novel peptide aldehydes as inhibitors of 20s proteasome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264673/
https://www.ncbi.nlm.nih.gov/pubmed/21894088
http://dx.doi.org/10.3390/molecules16097551
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