Zanamivir衍生物作為流感病毒抑制劑之開發及氟標記結合化學酶合成寡醣的研究與探討

林建宏

3.236.75.30，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

Basic & Applied Sciences > Chemistry
College of Science > Department of Chemistry

Bibliography Management Tool

Related Links

Report an Issue

Search in Library

There is no full-text available at the moment. Airiti would like to request author's authorization. I would like to provide authorization.

Zanamivir衍生物作為流感病毒抑制劑之開發及氟標記結合化學酶合成寡醣的研究與探討

Development of Zanamivir Analogs as Inhibitors of Influenza virus and Fluorous Tag Assisted Chemo-enzymatic Synthesis of Oligosaccharides

林建宏 , Ph.D　　Advisor：林俊成　　

繁體中文

流感抑制劑；氟標記；化學酶合成；合成寡醣； zanamivir ； Fluorous Tag ； Synthesis of Oligosaccharides ； Chemo-enzymatic

Abstract │ Reference (150) │ Times Cited (1) │ Altmetrics

Abstract 〈TOP〉

Parallel Abstract 〈TOP〉

Influenza virus is the cause of major respiratory illness in human populations, and the trimeric viral hemagglutinin (HA) and neuraminidase (NA) proteins are the two most prominent antigens targeted by the host immune system. The design and synthesis of NA inhibitors is a subject of intense research owing to both the recent outbreaks of avian influenza and the emergence of viruses that are highly resistant to widely used drugs. In this study, a series of acylguanidine-modified zanamivir analogs (~40 analogs) were synthesized, and their inhibitory activities against the NAs of avian influenza viruses (H1N1 and H3N2) were evaluated. In particular, zanamivir derivative 3j, with a hydrophobic naphthalene substituent, exhibits the best inhibitory activity against group-1 NA, with an IC50 of 20 nM. Our results show that the average IC50 values of these zanamivir derivatives are in the nanomolar range, indicating the importance of both the carbonyl group, which can generate additional contacts through hydrogen bonding with the E119 and D151 residues of NA, and the hydrophobic group, which may interact with the adjacent 150 cavity. Our results provide information that may aid in the development of more potent neuraminidase inhibitors.
Enzymatic synthesis is suitable for synthesizing complex oligosaccharides. However, tedious purification step often lead to a low overall yield and costs a lot of time. Therefore, a simple and effective method, synthetically viable to complex glycan structures circumventing the need of labor-intensive and time-consuming purification steps is highly desirable. To address this, here, we have developed a new purification technique of carbohydrates in combination with photolysis and enzymatic synthesis by incorporating a fluorous tag at the reducing end of glycans. In this study, we are successful to synthesize oligosaccharides, such as Sialyl Lewis X (SLex) and poly-LacNAc. We first synthesized the fluorous tag containing N-acetylglucosamine by chemical synthesis, and the carbohydrate chains were elongated at the non-reducing end by employing transferases, such as thymidylyltransferase (RmlA), N-acetylhexosamine-1-kinase (NahK), β-1,3-N-acetyl-glucosaminyltransferase (HpGnT), β-1,4-galactosyltransferase (NmGalT), α-1,4-galactosyltransferase (LgtC), and α-2,3-sialyltransferase (Cst I), and α-1,3-fucosyltransferas (FucT). Furthermore, we also developed a diverse glycan library through the fluorous tag.

Reference ( 150 ) 〈TOP〉

1. Steinhauer, D. A.; Skehel, J. J., Genetics of influenza viruses. Annu. Rev. Genet. 2002, 36, 305-332.
連結：
2. Lee, C.-W.; Saif, Y. M., Avian influenza virus. Comp. Immunol. Microbiol. Infect. Dis. 2009, 32, 301-310.
連結：
3. Webster, R. G., 1918 Spanish influenza: The secrets remain elusive. Proc. Natl. Acad. Sci. U. S. A. 1999, 96, 1164-1166.
連結：
5. Kasson, P. M.; Ensign, D. L.; Pande, V. S., Combining Molecular Dynamics with Bayesian Analysis To Predict and Evaluate Ligand-Binding Mutations in Influenza Hemagglutinin. J. Am. Chem. Soc. 2009, 131, 11338-11340.
連結：
6. Subbarao, K.; Joseph, T., Scientific barriers to developing vaccines against avian influenza viruses. Nat. Rev. Immunol. 2007, 7, 267-278.
連結：

Times Cited (1) 〈TOP〉

侯凱齡(2013)。利用氟標記輔助化學及酵素合成寡醣。清華大學化學系所學位論文。2013。1-130。

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：