Bioprospecting a medicinal plant for therapeutics

Eleutherococcus trifoliatus, a valuable medicinal plant, has been used to treat injuries and diseases for centuries. Its orally active decoction may have the presence of cysteine-rich peptides (CRPs), a 2-6 kDa, functionally diverse and hyperdisulfide mini-proteins that have therapeutic relevance. T...

Full description

Bibliographic Details
Main Author: Ho, Malcolm Zheng Hao
Other Authors: James P Tam
Format: Final Year Project (FYP)
Language:English
Published: Nanyang Technological University 2020
Subjects:
Online Access:https://hdl.handle.net/10356/140947
_version_ 1826122468037754880
author Ho, Malcolm Zheng Hao
author2 James P Tam
author_facet James P Tam
Ho, Malcolm Zheng Hao
author_sort Ho, Malcolm Zheng Hao
collection NTU
description Eleutherococcus trifoliatus, a valuable medicinal plant, has been used to treat injuries and diseases for centuries. Its orally active decoction may have the presence of cysteine-rich peptides (CRPs), a 2-6 kDa, functionally diverse and hyperdisulfide mini-proteins that have therapeutic relevance. This study reports the discovery, characterisation and therapeutic bioprospection of a CRP termed eleutherotide eT3670 extracted from E. trifoliatus. eT3670 consists of 35 amino acids and possesses an 8C-cysteine motif potentially forming six inter- cysteine loops via four intramolecular disulfide bonds that confer it resistance to thermal, acidic, enzymatic and serum-mediated degradation. Transcriptomic and bioinformatics analyses revealed that eT3670 is synthesised as a three-domain precursor, its disulfide connectivity as Cys I-IV, II-VI, III-VII, V-VIII, its inter-cysteine loops tolerance to amino acid variation and that it contains a variant LC3-interacting region motif related to selective autophagy. Cell-based assays showed that eT3670 is cytoprotective and a potential adaptogen that may induce autophagy to maintain cellular homeostasis, protecting cells from hypoxia stress-mediated damage and cell death. Together, the study bioprospects eT3670 as a potential candidate to be developed as a stable orally active drug for the treatment of autophagy-related diseases and as a grafting scaffold to enhance the stability of peptidyl therapeutics.
first_indexed 2024-10-01T05:48:39Z
format Final Year Project (FYP)
id ntu-10356/140947
institution Nanyang Technological University
language English
last_indexed 2024-10-01T05:48:39Z
publishDate 2020
publisher Nanyang Technological University
record_format dspace
spelling ntu-10356/1409472023-02-28T18:08:38Z Bioprospecting a medicinal plant for therapeutics Ho, Malcolm Zheng Hao James P Tam School of Biological Sciences JPTam@ntu.edu.sg Science::Biological sciences Eleutherococcus trifoliatus, a valuable medicinal plant, has been used to treat injuries and diseases for centuries. Its orally active decoction may have the presence of cysteine-rich peptides (CRPs), a 2-6 kDa, functionally diverse and hyperdisulfide mini-proteins that have therapeutic relevance. This study reports the discovery, characterisation and therapeutic bioprospection of a CRP termed eleutherotide eT3670 extracted from E. trifoliatus. eT3670 consists of 35 amino acids and possesses an 8C-cysteine motif potentially forming six inter- cysteine loops via four intramolecular disulfide bonds that confer it resistance to thermal, acidic, enzymatic and serum-mediated degradation. Transcriptomic and bioinformatics analyses revealed that eT3670 is synthesised as a three-domain precursor, its disulfide connectivity as Cys I-IV, II-VI, III-VII, V-VIII, its inter-cysteine loops tolerance to amino acid variation and that it contains a variant LC3-interacting region motif related to selective autophagy. Cell-based assays showed that eT3670 is cytoprotective and a potential adaptogen that may induce autophagy to maintain cellular homeostasis, protecting cells from hypoxia stress-mediated damage and cell death. Together, the study bioprospects eT3670 as a potential candidate to be developed as a stable orally active drug for the treatment of autophagy-related diseases and as a grafting scaffold to enhance the stability of peptidyl therapeutics. Bachelor of Science in Biological Sciences 2020-06-03T03:15:00Z 2020-06-03T03:15:00Z 2020 Final Year Project (FYP) https://hdl.handle.net/10356/140947 en application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences
Ho, Malcolm Zheng Hao
Bioprospecting a medicinal plant for therapeutics
title Bioprospecting a medicinal plant for therapeutics
title_full Bioprospecting a medicinal plant for therapeutics
title_fullStr Bioprospecting a medicinal plant for therapeutics
title_full_unstemmed Bioprospecting a medicinal plant for therapeutics
title_short Bioprospecting a medicinal plant for therapeutics
title_sort bioprospecting a medicinal plant for therapeutics
topic Science::Biological sciences
url https://hdl.handle.net/10356/140947
work_keys_str_mv AT homalcolmzhenghao bioprospectingamedicinalplantfortherapeutics