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|Title:||Discovery and characterization of novel peptide biologics in herbal medicine||Authors:||Nguyen, Kien Truc Giang||Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2011||Source:||Nguyen, K. T. G. (2011). Discovery and characterization of novel peptide biologics in herbal medicine. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||Peptide and protein biologics are therapeutics and prophylactics known for their desirability of high specificity and low toxicity. They display a wide range of biological activities such as antimicrobial, immunomodulation, neurotransmission and hormonal functions. Most biologics are derived from animal sources with few representatives from plants. In herbal medicine, these biologics have not received much attention with the common perception that they are unstable and unavailable as a source of active principles in decoctions. This bias is explained by the intrinsic instability of peptides and proteins during the concoctions preparation, poor absorption through the gastrointestinal tract and their susceptibility to enzymatic and acidic hydrolysis under harsh environment inside our stomach. My hypothesis is that plant biologics may constitute a group of unexplored active principles in traditional herbal medicine. Research in this thesis focuses on plant cysteine-rich peptides (CRPs) such as cyclotides, uncyclotides, knottins, heveins and plant defensins. These peptides have recently gained great interest among the scientific community due to their remarkable stability and diverse biological functions. The major aims of this project are: (1) discovery of novel biologics from medicinal plants using tandem mass spectrometry, (2) characterization of their thermal and enzymatic stabilities, tissue specificity, genetic structures and disulfide connectivities, (3) pharmacological profilings of their biological activities for therapeutic applications. The proposed study may provide lead compounds for drug development and aid in quantitative profiling of active ingredients in commercial viable medicinal herbs. In this thesis, I have successfully identified more than 120 novel peptides comprising of cyclotides, uncyclotides, defensins and various CRPs from several medicinally important plants. By far only four uncyclotides have been reported, and thus the discovery of over 20 uncyclotides in this work is a surprising and provides insights about the biosynthetic processing of cyclic peptides. I also provide the first description of defensin-like peptides in cyclotide-producing plants. In addition, two novel classes of cysteine-rich peptides, ginsentide and morintide, have been identified from ginseng and Morinda citrifolia, respectively. Furthermore, I also expand the distribution of cyclotides to a new plant family, the Fabaceae. Biophysical characterization of novel CRPs showed that most of them display high stability against heat and enzymatic digestions together with their amphipathic structures making them the likely active principles in herbal medicine. Activity screenings showed that many CRPs display potent antimicrobial, cytotoxic and hemolytic properties. Biologics with interesting pharmacological profiles could be used as lead compounds for drug development.||URI:||https://hdl.handle.net/10356/46476||DOI:||10.32657/10356/46476||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Theses|
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