Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor

Cysteine-rich peptides (CRPs) are a group of underexplored compounds between 2 – 8 kDa. Hibiscus sabdariffa was found to be a rich source of CRPs which were named as roseltides. Thus far, eight roseltides rT1 – rT8 have been identified. Roseltide rT1 was previously characterized as a knottin-type hu...

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Main Author: Chan, Leonard Huang Yoon
Other Authors: James P. Tam
Format: Final Year Project
Language:English
Published: 2018
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Online Access:http://hdl.handle.net/10356/76199
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-761992023-02-28T18:06:38Z Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor Chan, Leonard Huang Yoon James P. Tam School of Biological Sciences DRNTU::Science::Biological sciences Cysteine-rich peptides (CRPs) are a group of underexplored compounds between 2 – 8 kDa. Hibiscus sabdariffa was found to be a rich source of CRPs which were named as roseltides. Thus far, eight roseltides rT1 – rT8 have been identified. Roseltide rT1 was previously characterized as a knottin-type human neutrophil elastase inhibitor. The second most abundant, roseltide rT7 however, have not been characterized. In this study, we aim to chemically synthesize and functionally characterize roseltide rT7. Here we report the successful synthesis of roseltide rT7 using automated solid-phase peptide synthesis followed by oxidative folding of the linear peptide into its native conformation. Using chemical labeling, we successfully obtained TAMRA-rT7 which displayed cell-penetrating properties in flow cytometry and confocal microscopy analyses. Sequence motif search revealed roseltide rT7 shared sequence similarity to PR-39, a cell-penetrating proteasome inhibitor with pro-angiogenic properties. Likewise in this study, roseltide rT7 was found to be a 20S proteasome inhibitor and possess pro-angiogenic properties. To the best of our knowledge, roseltide rT7 is a “first-in-class” cystine-stabilized proteasome inhibitor with pro-angiogenic properties. Bachelor of Science in Biological Sciences 2018-11-29T01:53:28Z 2018-11-29T01:53:28Z 2018 Final Year Project (FYP) http://hdl.handle.net/10356/76199 en Nanyang Technological University 33 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Chan, Leonard Huang Yoon
Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
description Cysteine-rich peptides (CRPs) are a group of underexplored compounds between 2 – 8 kDa. Hibiscus sabdariffa was found to be a rich source of CRPs which were named as roseltides. Thus far, eight roseltides rT1 – rT8 have been identified. Roseltide rT1 was previously characterized as a knottin-type human neutrophil elastase inhibitor. The second most abundant, roseltide rT7 however, have not been characterized. In this study, we aim to chemically synthesize and functionally characterize roseltide rT7. Here we report the successful synthesis of roseltide rT7 using automated solid-phase peptide synthesis followed by oxidative folding of the linear peptide into its native conformation. Using chemical labeling, we successfully obtained TAMRA-rT7 which displayed cell-penetrating properties in flow cytometry and confocal microscopy analyses. Sequence motif search revealed roseltide rT7 shared sequence similarity to PR-39, a cell-penetrating proteasome inhibitor with pro-angiogenic properties. Likewise in this study, roseltide rT7 was found to be a 20S proteasome inhibitor and possess pro-angiogenic properties. To the best of our knowledge, roseltide rT7 is a “first-in-class” cystine-stabilized proteasome inhibitor with pro-angiogenic properties.
author2 James P. Tam
author_facet James P. Tam
Chan, Leonard Huang Yoon
format Final Year Project
author Chan, Leonard Huang Yoon
author_sort Chan, Leonard Huang Yoon
title Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
title_short Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
title_full Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
title_fullStr Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
title_full_unstemmed Discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
title_sort discovery of a "first-in-class" plant-derived cystine-stabilized proteasome inhibitor
publishDate 2018
url http://hdl.handle.net/10356/76199
_version_ 1759856925742202880