國立高雄大學圖資館 |

語系: 繁體中文

說明(常見問題)

圖資館首頁

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Investigations into Bioactive Second...

Mevers, Emily.

Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria.
作者:	Mevers, Emily.
面頁冊數:	329 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.
附註:	Adviser: William H. Gerwick.
Contained By:	Dissertation Abstracts International75-07B(E).
標題:	Organic chemistry.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3615750
ISBN:	9781303818318

Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria.
Mevers, Emily.

Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria. - 329 p.

Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.

Thesis (Ph.D.)--University of California, San Diego, 2014.

This item is not available from ProQuest Dissertations & Theses.

Marine cyanobacteria are prolific producers of structurally intriguing and biologically important secondary metabolites, many of which are of mixed NRPS/PKS biosynthetic origins, and have a broad range of biological activity, including ion channel modulation, cancer cell toxicity, anti-parasitic, anti-bacterial, anti-inflammatory, brine shrimp toxicity, and molluscicidal. Presently, there is one clinically approved drug that is an analog of the cyanobacterial natural product, dolastatin 10, while there are several agents in clinical trial, including soblidotin and synthadotin, which are analogs of dolastatin 15 and 10, respectively. Additionally, others are currently undergoing preclinical evaluation as anti-cancer agents, including apratoxin F, curacin A, desmethoxymajusculamide C (DMMC) and somacystinamide. The primary research objective of the research herein was to isolate and elucidate the structures of biologically active secondary metabolites from tropical marine cyanobacteria. In total, fifteen novel compounds from either Oscillatoria or Moorea were isolated and characterized. These include thirteen highly modified peptides (veraguamides A-C and H-L, precarriebowmide, tasiamides C-E, and lyngbyabellin N) and two alkyl amides (parguerene and mooreamide). The planar structure elucidation of each of these metabolites involved the use of 2D NMR spectroscopy and mass spectrometry techniques, including a mass spectrometry based dereplication algorithm to deduce the planar structure of several of the modified peptides. Absolute stereochemical analysis involved many techniques, such as Marfey's analysis, semisynthesis, 3J coupling constant analysis, circular dichroism, 13C NMR comparisions, NOE correlations, and chiral GCMS analysis. Many of these compounds were biologically evaluated with veraguamide A and lyngbyabellin N exhibiting cancer cell cytotoxicity [IC50 = 141 nM (H-460) and IC50 = 40.9 (HCT-116), respectively], and mooreamide exhibiting cannabinoid receptor binding activity (Ki = 0.47 muM). A secondary research objective has been the structure-activity relationship (SAR) study to investigate the active pharmacophore in the lyngbyamide family of compounds, which consist of a cyclopropyl fatty acid (tail) and an amide head group. In total, 50 analogs were synythesized, designed to probe the importance of several structural characteristics of the lyngbyamides. These compounds were tested in a wide array of biological assays, and a subset were found to possess strong activity in the stabilization of cathepsin L-mediated proteolysis, brine shrimp toxicity, and surface tension suppression.

ISBN: 9781303818318Subjects--Topical Terms:

708640
Organic chemistry.

Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria.
LDR:03714nmm a2200313 4500 001 457651
005 20150805065215.5
008 150916s2014 ||||||||||||||||| ||eng d
020 $a 9781303818318
035 $a (MiAaPQ)AAI3615750
035 $a AAI3615750
040 $a MiAaPQ $c MiAaPQ
100 1 $a Mevers, Emily. $3 708639
245 1 0 $a Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria.
300 $a 329 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-07(E), Section: B.
500 $a Adviser: William H. Gerwick.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2014.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
520 $a Marine cyanobacteria are prolific producers of structurally intriguing and biologically important secondary metabolites, many of which are of mixed NRPS/PKS biosynthetic origins, and have a broad range of biological activity, including ion channel modulation, cancer cell toxicity, anti-parasitic, anti-bacterial, anti-inflammatory, brine shrimp toxicity, and molluscicidal. Presently, there is one clinically approved drug that is an analog of the cyanobacterial natural product, dolastatin 10, while there are several agents in clinical trial, including soblidotin and synthadotin, which are analogs of dolastatin 15 and 10, respectively. Additionally, others are currently undergoing preclinical evaluation as anti-cancer agents, including apratoxin F, curacin A, desmethoxymajusculamide C (DMMC) and somacystinamide. The primary research objective of the research herein was to isolate and elucidate the structures of biologically active secondary metabolites from tropical marine cyanobacteria. In total, fifteen novel compounds from either Oscillatoria or Moorea were isolated and characterized. These include thirteen highly modified peptides (veraguamides A-C and H-L, precarriebowmide, tasiamides C-E, and lyngbyabellin N) and two alkyl amides (parguerene and mooreamide). The planar structure elucidation of each of these metabolites involved the use of 2D NMR spectroscopy and mass spectrometry techniques, including a mass spectrometry based dereplication algorithm to deduce the planar structure of several of the modified peptides. Absolute stereochemical analysis involved many techniques, such as Marfey's analysis, semisynthesis, 3J coupling constant analysis, circular dichroism, 13C NMR comparisions, NOE correlations, and chiral GCMS analysis. Many of these compounds were biologically evaluated with veraguamide A and lyngbyabellin N exhibiting cancer cell cytotoxicity [IC50 = 141 nM (H-460) and IC50 = 40.9 (HCT-116), respectively], and mooreamide exhibiting cannabinoid receptor binding activity (Ki = 0.47 muM). A secondary research objective has been the structure-activity relationship (SAR) study to investigate the active pharmacophore in the lyngbyamide family of compounds, which consist of a cyclopropyl fatty acid (tail) and an amide head group. In total, 50 analogs were synythesized, designed to probe the importance of several structural characteristics of the lyngbyamides. These compounds were tested in a wide array of biological assays, and a subset were found to possess strong activity in the stabilization of cathepsin L-mediated proteolysis, brine shrimp toxicity, and surface tension suppression.
590 $a School code: 0033.
650 4 $a Organic chemistry. $3 708640
650 4 $a Biochemistry. $3 188609
650 4 $a Chemistry. $3 188628
690 $a 0490
690 $a 0487
690 $a 0485
710 2 $a University of California, San Diego. $b Chemistry. $3 531004
773 0 $t Dissertation Abstracts International $g 75-07B(E).
790 $a 0033
791 $a Ph.D.
792 $a 2014
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3615750