Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants
Medicinal plants showed great importance in managing and treating human diseases. Currently, plant-derived small-molecule metabolites with molecular weight (M.W.) <1 kDa are major active components that account for approximately 46% of all the clinically approved drugs. Another major family of...
Saved in:
Main Author: | |
---|---|
Other Authors: | |
Format: | Thesis-Doctor of Philosophy |
Language: | English |
Published: |
Nanyang Technological University
2020
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/137776 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-137776 |
---|---|
record_format |
dspace |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
Science::Biological sciences::Biochemistry Science::Chemistry::Analytical chemistry |
spellingShingle |
Science::Biological sciences::Biochemistry Science::Chemistry::Analytical chemistry Huang, Jiayi Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
description |
Medicinal plants showed great importance in managing and treating human diseases. Currently,
plant-derived small-molecule metabolites with molecular weight (M.W.) <1 kDa are major
active components that account for approximately 46% of all the clinically approved drugs.
Another major family of pharmaceuticals that have been extensively studied and used clinically
is proteins with M.W. >10 kDa. However, few peptidyl products which occupy the chemical
space between metabolites and proteins are clinically approved as drugs. Typically, peptides
are susceptible to harsh conditions and have poor bioavailability. Disulfide-constrained
cysteine-rich peptides (CRPs) are a family of molecules with highly compact structures, in a
particular range of M.W. from 2 – 6 kDa. These disulfide bridges confer them the stability
against thermal, acidic and enzymatic degradation. Currently, these naturally-occurring
disulfide-constrained peptides are highly under-explored in medicinal plants.
Another vital issue for herbal medicines is the misidentification of plant species and the
presence of adulterants. The traditional authentication method using chromatographic
fingerprinting is precise, sensitive, and reproducible. However, laborious sample preparation,
relatively long analytical run-times, and the large volume of organic solvents consumption in
HPLC hinders its application as a high-throughput screening technique. Hence, the
development of a rapid and accurate quality control method is urgently needed.
My thesis aims to discover and characterize CRPs from medicinal plants and to apply them in
the authentication of herbal medicines. A general and rapid method, which employs CRPs as
unique chemical markers for the authentication of herbal medicines, was described in this thesis.
This CRP fingerprinting method produces consistent results for herbal authentication
regardless of the morphology, chemical composition, and origins of the plant species. The
differentiation of two similar species, Radix Astragali and Radix Hedysarum, was used as an
example to validate the method. Coupling with multivariate analyses, the study showed that
CRP fingerprinting is fast, and the classification accuracy is comparable to that of the
conventional authentication method using UPLC. To further understand the usefulness and
functions of CRPs, clusters of CRPs discovered from medicinal plants and important crops
were studied. They include CRPs from Coffea canephora and Coffea liberica, which are plants
with medicinal values used to produce the second-largest commodity, coffee drinks. Proteomic
and transcriptomic analyses showed that coffeetides identified from the Coffea species are nonchitin-
binding hevein-like peptides. Another group of CRPs was identified from the roots of
Astragalus membranaceus (Fisch.) Bje, which is a traditional Chinese medicine for improving overall vitality and treating diabetes. Two different types of CRPs were identified in this plant
and designated as α- and β-astratides. NMR spectroscopy, bioinformatics analysis, and
functional bioassays were used to determine the structure, evolutionary relationship, and
functions of all these CRPs. Taken together, my thesis expanded the existing library of CRPs
and explored their potential for drug design and their usefulness as fingerprints for the
authentication of herbal medicine. |
author2 |
James P Tam |
author_facet |
James P Tam Huang, Jiayi |
format |
Thesis-Doctor of Philosophy |
author |
Huang, Jiayi |
author_sort |
Huang, Jiayi |
title |
Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
title_short |
Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
title_full |
Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
title_fullStr |
Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
title_full_unstemmed |
Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
title_sort |
discovery, characterization, and applications of cysteine-rich peptides from medicinal plants |
publisher |
Nanyang Technological University |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/137776 |
_version_ |
1759853913544065024 |
spelling |
sg-ntu-dr.10356-1377762023-02-28T18:34:27Z Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants Huang, Jiayi James P Tam School of Biological Sciences JPTam@ntu.edu.sg Science::Biological sciences::Biochemistry Science::Chemistry::Analytical chemistry Medicinal plants showed great importance in managing and treating human diseases. Currently, plant-derived small-molecule metabolites with molecular weight (M.W.) <1 kDa are major active components that account for approximately 46% of all the clinically approved drugs. Another major family of pharmaceuticals that have been extensively studied and used clinically is proteins with M.W. >10 kDa. However, few peptidyl products which occupy the chemical space between metabolites and proteins are clinically approved as drugs. Typically, peptides are susceptible to harsh conditions and have poor bioavailability. Disulfide-constrained cysteine-rich peptides (CRPs) are a family of molecules with highly compact structures, in a particular range of M.W. from 2 – 6 kDa. These disulfide bridges confer them the stability against thermal, acidic and enzymatic degradation. Currently, these naturally-occurring disulfide-constrained peptides are highly under-explored in medicinal plants. Another vital issue for herbal medicines is the misidentification of plant species and the presence of adulterants. The traditional authentication method using chromatographic fingerprinting is precise, sensitive, and reproducible. However, laborious sample preparation, relatively long analytical run-times, and the large volume of organic solvents consumption in HPLC hinders its application as a high-throughput screening technique. Hence, the development of a rapid and accurate quality control method is urgently needed. My thesis aims to discover and characterize CRPs from medicinal plants and to apply them in the authentication of herbal medicines. A general and rapid method, which employs CRPs as unique chemical markers for the authentication of herbal medicines, was described in this thesis. This CRP fingerprinting method produces consistent results for herbal authentication regardless of the morphology, chemical composition, and origins of the plant species. The differentiation of two similar species, Radix Astragali and Radix Hedysarum, was used as an example to validate the method. Coupling with multivariate analyses, the study showed that CRP fingerprinting is fast, and the classification accuracy is comparable to that of the conventional authentication method using UPLC. To further understand the usefulness and functions of CRPs, clusters of CRPs discovered from medicinal plants and important crops were studied. They include CRPs from Coffea canephora and Coffea liberica, which are plants with medicinal values used to produce the second-largest commodity, coffee drinks. Proteomic and transcriptomic analyses showed that coffeetides identified from the Coffea species are nonchitin- binding hevein-like peptides. Another group of CRPs was identified from the roots of Astragalus membranaceus (Fisch.) Bje, which is a traditional Chinese medicine for improving overall vitality and treating diabetes. Two different types of CRPs were identified in this plant and designated as α- and β-astratides. NMR spectroscopy, bioinformatics analysis, and functional bioassays were used to determine the structure, evolutionary relationship, and functions of all these CRPs. Taken together, my thesis expanded the existing library of CRPs and explored their potential for drug design and their usefulness as fingerprints for the authentication of herbal medicine. Doctor of Philosophy 2020-04-14T05:45:24Z 2020-04-14T05:45:24Z 2019 Thesis-Doctor of Philosophy Huang, J. (2019). Discovery, characterization, and applications of cysteine-rich peptides from medicinal plants. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/137776 10.32657/10356/137776 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University |