語系:
繁體中文
English
說明(常見問題)
回圖書館首頁
手機版館藏查詢
登入
回首頁
切換:
標籤
|
MARC模式
|
ISBD
FindBook
Google Book
Amazon
博客來
Engineering Enzymes for Selective Detection and Degradation of Mucins.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Engineering Enzymes for Selective Detection and Degradation of Mucins./
作者:
Shon, Dayeon Judy.
面頁冊數:
1 online resource (162 pages)
附註:
Source: Dissertations Abstracts International, Volume: 84-12, Section: A.
Contained By:
Dissertations Abstracts International84-12A.
標題:
Physiology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30462702click for full text (PQDT)
ISBN:
9798379652883
Engineering Enzymes for Selective Detection and Degradation of Mucins.
Shon, Dayeon Judy.
Engineering Enzymes for Selective Detection and Degradation of Mucins.
- 1 online resource (162 pages)
Source: Dissertations Abstracts International, Volume: 84-12, Section: A.
Thesis (Ph.D.)--Stanford University, 2023.
Includes bibliographical references
Every cell in the human body harbors a dense outer layer of carbohydrates, or glycans, that serves as an interface for cell surface communication. This peripheral structure, known as the glycocalyx, influences cell-cell and cell-matrix interactions through a dense network of glycoproteins, glycolipids, and proteoglycans. These glycans are essential for a wide range of physiological processes, and defects in glycosylation often contribute to human disease. In this work, we focus on mucins, which carry densely O-glycosylated domains found in many cell surface and secreted proteins. As introduced in Chapter 1, alterations in mucin expression and glycosylation are common in a variety of diseases such as cancer and cystic fibrosis. These correlations have motivated efforts towards the therapeutic targeting of disease-associated mucins and their aberrant glycoforms. However, the precise contexts in which mucins and their glycans contribute to disease progression remain unclear, due to difficulties associated with their detection and a lack of tools that specifically probe mucin domains. In Chapter 2, we address this limitation by characterizing a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. We further develop catalytically inactive mutants and demonstrate robust detection of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry, enabling a new depth in the analysis of mucins on cells and patient tissues. In Chapter 3, we characterize a mucin-selective metalloprotease from Akkermansia muciniphila via X-ray crystallography and molecular modeling to gain insight into the structural determinants of O-glycan recognition. Finally, in Chapter 4, we develop a targeted degradation strategy to selectively remove cancer-associated mucins by fusing an engineered mucin-selective protease to a cancer antigen-binding nanobody. We show that these targeted proteases reduce cancer cell viability in vitro and blunt primary tumor burden and metastatic outgrowth in murine breast cancer models. As nearly all extracellular proteins are glycosylated and glycosylation status is commonly altered in disease, glycoform-dependent and cell type-selective targeted protein degradation presents a general opportunity for increasing on-target specificity for disease-driving extracellular proteins.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023
Mode of access: World Wide Web
ISBN: 9798379652883Subjects--Topical Terms:
518431
Physiology.
Index Terms--Genre/Form:
542853
Electronic books.
Engineering Enzymes for Selective Detection and Degradation of Mucins.
LDR
:03846nmm a2200409K 4500
001
2363007
005
20231109104731.5
006
m o d
007
cr mn ---uuuuu
008
241011s2023 xx obm 000 0 eng d
020
$a
9798379652883
035
$a
(MiAaPQ)AAI30462702
035
$a
(MiAaPQ)STANFORDjh002rv3213
035
$a
AAI30462702
040
$a
MiAaPQ
$b
eng
$c
MiAaPQ
$d
NTU
100
1
$a
Shon, Dayeon Judy.
$3
3703753
245
1 0
$a
Engineering Enzymes for Selective Detection and Degradation of Mucins.
264
0
$c
2023
300
$a
1 online resource (162 pages)
336
$a
text
$b
txt
$2
rdacontent
337
$a
computer
$b
c
$2
rdamedia
338
$a
online resource
$b
cr
$2
rdacarrier
500
$a
Source: Dissertations Abstracts International, Volume: 84-12, Section: A.
500
$a
Advisor: Barnes, Christopher O.;Cui, Bianxiao;Bertozzi, Carolyn.
502
$a
Thesis (Ph.D.)--Stanford University, 2023.
504
$a
Includes bibliographical references
520
$a
Every cell in the human body harbors a dense outer layer of carbohydrates, or glycans, that serves as an interface for cell surface communication. This peripheral structure, known as the glycocalyx, influences cell-cell and cell-matrix interactions through a dense network of glycoproteins, glycolipids, and proteoglycans. These glycans are essential for a wide range of physiological processes, and defects in glycosylation often contribute to human disease. In this work, we focus on mucins, which carry densely O-glycosylated domains found in many cell surface and secreted proteins. As introduced in Chapter 1, alterations in mucin expression and glycosylation are common in a variety of diseases such as cancer and cystic fibrosis. These correlations have motivated efforts towards the therapeutic targeting of disease-associated mucins and their aberrant glycoforms. However, the precise contexts in which mucins and their glycans contribute to disease progression remain unclear, due to difficulties associated with their detection and a lack of tools that specifically probe mucin domains. In Chapter 2, we address this limitation by characterizing a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. We further develop catalytically inactive mutants and demonstrate robust detection of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry, enabling a new depth in the analysis of mucins on cells and patient tissues. In Chapter 3, we characterize a mucin-selective metalloprotease from Akkermansia muciniphila via X-ray crystallography and molecular modeling to gain insight into the structural determinants of O-glycan recognition. Finally, in Chapter 4, we develop a targeted degradation strategy to selectively remove cancer-associated mucins by fusing an engineered mucin-selective protease to a cancer antigen-binding nanobody. We show that these targeted proteases reduce cancer cell viability in vitro and blunt primary tumor burden and metastatic outgrowth in murine breast cancer models. As nearly all extracellular proteins are glycosylated and glycosylation status is commonly altered in disease, glycoform-dependent and cell type-selective targeted protein degradation presents a general opportunity for increasing on-target specificity for disease-driving extracellular proteins.
533
$a
Electronic reproduction.
$b
Ann Arbor, Mich. :
$c
ProQuest,
$d
2023
538
$a
Mode of access: World Wide Web
650
4
$a
Physiology.
$3
518431
650
4
$a
Glycoproteins.
$3
667972
650
4
$a
Metastasis.
$3
818532
650
4
$a
Disease.
$3
705846
650
4
$a
Families & family life.
$3
3422406
650
4
$a
E coli.
$3
3556834
650
4
$a
Flow cytometry.
$3
600581
650
4
$a
Lipids.
$3
558980
650
4
$a
Visualization.
$3
586179
650
4
$a
Breast cancer.
$3
3543523
650
4
$a
Ovarian cancer.
$3
3564639
650
4
$a
Patients.
$3
1961957
650
4
$a
Mass spectrometry.
$3
551172
650
4
$a
Cloning.
$3
571606
650
4
$a
Medical research.
$2
bicssc
$3
1556686
650
4
$a
Engineering.
$3
586835
650
4
$a
Surveillance.
$3
3559358
650
4
$a
Enzymes.
$3
520899
650
4
$a
Polypeptides.
$3
1085124
650
4
$a
Crystallography.
$3
518393
650
4
$a
Interfaces.
$2
gtt
$3
834756
650
4
$a
Analytical chemistry.
$3
3168300
650
4
$a
Cellular biology.
$3
3172791
650
4
$a
Chemistry.
$3
516420
650
4
$a
Individual & family studies.
$3
2122770
650
4
$a
Medicine.
$3
641104
650
4
$a
Oncology.
$3
751006
655
7
$a
Electronic books.
$2
lcsh
$3
542853
690
$a
0537
690
$a
0719
690
$a
0486
690
$a
0379
690
$a
0485
690
$a
0628
690
$a
0564
690
$a
0992
710
2
$a
ProQuest Information and Learning Co.
$3
783688
710
2
$a
Stanford University.
$3
754827
773
0
$t
Dissertations Abstracts International
$g
84-12A.
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30462702
$z
click for full text (PQDT)
筆 0 讀者評論
館藏地:
全部
電子資源
出版年:
卷號:
館藏
1 筆 • 頁數 1 •
1
條碼號
典藏地名稱
館藏流通類別
資料類型
索書號
使用類型
借閱狀態
預約狀態
備註欄
附件
W9485363
電子資源
11.線上閱覽_V
電子書
EB
一般使用(Normal)
在架
0
1 筆 • 頁數 1 •
1
多媒體
評論
新增評論
分享你的心得
Export
取書館
處理中
...
變更密碼
登入