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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 朱忠瀚(Chung-Han Chu) | |
| dc.contributor.author | Cheng-Han Wu | en |
| dc.contributor.author | 吳承翰 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:12:44Z | - |
| dc.date.available | 2021-11-04 | |
| dc.date.available | 2022-11-24T03:12:44Z | - |
| dc.date.copyright | 2021-11-04 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-20 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80681 | - |
| dc.description.abstract | 天然物為生物的次級代謝物，往往具有多樣的生物活性，為生物帶來生存演化上的優勢。然而傳統天然物的發現方式十分繁瑣，需經過發酵、萃取層析分離、活性篩選、結構鑑定等步驟。不僅如此，現有技術僅有1%的微生物易於在實驗室培養取得，且許多的生合成基因在實驗室培養條件下不表現，更加限制了科學家能探索的天然物。因此我們期望發展一套技術平台，結合生物資訊結構預測以及化學合成，快速有效地找尋具有生物活性的天然物，而本論文即是針對此兩項技術奠定基礎。 論文第一部分為與荷蘭瓦赫寧恩大學M. Medema教授的生物資訊團隊合作，針對他們提供的6個非核醣體肽合成酶中的腺苷酸化區進行活性測試，希望藉此增加生物資訊演算法的樣本數，以提高演算法對胺基酸受質預測的準確度。我們透過基因工程方式克隆得到了這6個重組蛋白酵素，提供它們三磷酸腺苷，量測其與20種胺基酸能否反應釋出焦磷酸分子，屆此了解這些非核醣體肽合成酶所相對應的胺基酸受質。 論文第二部分為開發新穎胜肽固相噻唑(thiazole)合成法。噻唑五員雜環為胜肽天然物中常見的特殊骨架，我們希望藉此增加胜肽固相合成法用於合成此類型天然物的廣度。在本論文中我們以Hantzsch法合成完全氧化態噻唑構築體並以胜肽固相合成法合成出我們選定的目標天然物：於2019年由W. Gerwick團隊於海洋綠藻德式藻屬(Derbesia sp.)分離的天然物Pagoamide A。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:12:44Z (GMT). No. of bitstreams: 1 U0001-1910202102030400.pdf: 10743013 bytes, checksum: 5da328419e493642bd7918d38ccb20d5 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "摘要 I Abstract II Content IV List of Figures VII List of Schemes IX List of Tables XI Abbreviations XII Chapter 1: Introduction 1 1.1 Nonribosomal peptides 1 1.1.1 Diverse structures of NRPs 1 1.1.2 Architecture and the biosynthesis mechanism of NRPSs 2 1.2 The specificity-conferring code of NRPS A domain 4 1.3 Synthetic-bioinformatic natural products, syn-BNPs 5 1.4 The aim of this study 6 Chapter 2: Inorganic pyophosphate release assay of 6 unpredictable NRPS adenylation domains 8 2.1 Introduction 8 2.1.1 The conserved structures of A domains 8 2.1.2 Assays for measurement of NRPS A domain activity 11 2.2 Result and discussion 13 2.2.1 PheA as the positive control of the assay 13 2.2.2 Bioinformatics research of six unpredictable NRPS A domains 14 2.2.3 Six A domain recombinant proteins expression and purification 16 2.2.4 EnzChek pyrophosphate release assay for six unpredictable A domains 17 2.3 Conclusion 18 Chapter 3: Total synthesis of pagoamide A and its antimicrobial activity 22 3.1 Introduction 22 3.1.1 Thiazole- and thiazoline-containing natural peptides 23 3.1.2 Thiazoline and thiazole biosynthesis in NRPs 24 3.1.3 Thiazoline and thiazole forming reactions in organic synthesis 25 3.1.4 Thiazoline and thiazole synthesis on solid-phase 29 3.1.5 Pagoamide A 32 3.2 Result and discussion 33 3.2.1 Retrosynthetic analysis of pagoamide A 33 3.2.2 Synthesis of thiazole-containing and ester linkage dipeptide building blocks 34 3.2.3 Solid-phase synthesis of the linear precursor 21 and macrocyclization to afford pagoamide A 36 3.2.4 Structural determination 41 3.2.5 Antimicrobial assay 42 3.3 Conclusion 44 Chapter 4: Experimental Section 45 4.1 General information 45 4.2 Inorganic phosphate release assay of A domains 45 4.2.1 Protein expression and purification 45 4.2.2 EnzChek pyrophosphate assay 46 4.3 Total synthesis of pagoamide A and its antimicrobial activity 47 4.3.1 Chemical synthesis 47 4.3.2 General procedure for solid-phase synthesis: 56 4.3.3 Antimicrobial assays 59 References 60 Appendix 69 " | |
| dc.language.iso | en | |
| dc.subject | 噻唑合成法 | zh_TW |
| dc.subject | 非核醣體肽 | zh_TW |
| dc.subject | 非核醣體肽結構預測 | zh_TW |
| dc.subject | 胜肽固相合成法 | zh_TW |
| dc.subject | Nonribosomal peptide | en |
| dc.subject | NRPS adenylation domain | en |
| dc.subject | SPPS | en |
| dc.subject | Thiazole | en |
| dc.title | 非核醣體肽的化學及生物合成之研究 | zh_TW |
| dc.title | Chemical Synthesis and Biosynthetic Studies of Nonribosomal Peptide | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 方俊民(Hsin-Tsai Liu),羅禮強(Chih-Yang Tseng),謝俊結 | |
| dc.subject.keyword | 非核醣體肽,非核醣體肽結構預測,胜肽固相合成法,噻唑合成法, | zh_TW |
| dc.subject.keyword | Nonribosomal peptide,NRPS adenylation domain,SPPS,Thiazole, | en |
| dc.relation.page | 87 | |
| dc.identifier.doi | 10.6342/NTU202103857 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-21 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| Appears in Collections: | 化學系 | |
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| U0001-1910202102030400.pdf Access limited in NTU ip range | 10.49 MB | Adobe PDF |
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