| LDR | | 03371nmm uu200481 4500 |
| 001 | | 000000334553 |
| 005 | | 20240805180533 |
| 008 | | 181129s2016 |||||||||||||||||c||eng d |
| 020 | |
▼a 9780438159518 |
| 035 | |
▼a (MiAaPQ)AAI10251595 |
| 035 | |
▼a (MiAaPQ)wisc:14170 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 248032 |
| 082 | 0 |
▼a 574 |
| 100 | 1 |
▼a Smith, Thomas P. |
| 245 | 10 |
▼a Biomedical Applications and Strategies Using Boronic Acids. |
| 260 | |
▼a [S.l.] :
▼b The University of Wisconsin - Madison.,
▼c 2016 |
| 260 | 1 |
▼a Ann Arbor :
▼b ProQuest Dissertations & Theses,
▼c 2016 |
| 300 | |
▼a 358 p. |
| 500 | |
▼a Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B. |
| 500 | |
▼a Adviser: Ronald T. Raines. |
| 502 | 1 |
▼a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016. |
| 520 | |
▼a Boronic acids have been shown to interact with biological molecules including carbohydrates and reactive oxygen species (ROS). This variety of biological targets is due to the unique reactivity of boron that, within a physiological pH range, can |
| 520 | |
▼a The development of therapeutic proteins is generating considerable interest. This interest is due to the high selectivity of proteins for a target and the high enzymatic activity a protein-based therapeutic can possess. There are, however, a num |
| 520 | |
▼a In chapter 2, I describe the development of a discreet, small-molecule boronic acid-based delivery strategy for the delivery of native protein into the cytosol of a cell. This was accomplished by appending a specialized boronic acid directly to |
| 520 | |
▼a Another challenge with biologic therapeutics is overcoming the potential pleiotropic nature of the particular protein or enzyme. This challenge is explicit in the use of angiogenin (ANG) as a potential treatment of amyotrophic lateral sclerosis |
| 520 | |
▼a In chapter 3, I highlight a specific masking strategy that silences the catalytic activity of ANG under normal physiological conditions. When exposed to reactive oxygen species (ROS) leading to oxidative stress, this mask is removed, and catalyt |
| 520 | |
▼a In ALS, the up-regulation of ROS in the central nervous system (CNS) is primarily responsible for the motor neuron degeneration characteristic of the disease. The presence of a boronic acid-masking agent engenders ANG with pro-drug characteristi |
| 520 | |
▼a Boronic acids have also been utilized as important functional groups in medicinal chemistry. For example, VelcadeRTM (bortezomib), is a first-in-class boronic acid-containing protease inhibitor and the first boronic acid drug to be approved by t |
| 520 | |
▼a In chapter 4, I discuss the development and characterization of a targeted library of small-molecule boronic acids that bind to the thyroxin (T 4) binding pockets and strongly inhibit fibril formation in both wild-type and a common disease varia |
| 590 | |
▼a School code: 0262. |
| 650 | 4 |
▼a Biochemistry. |
| 650 | 4 |
▼a Chemistry. |
| 690 | |
▼a 0487 |
| 690 | |
▼a 0485 |
| 710 | 20 |
▼a The University of Wisconsin - Madison.
▼b Chemistry. |
| 773 | 0 |
▼t Dissertation Abstracts International
▼g 79-11B(E). |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0262 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2016 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T14996547
▼n KERIS |
| 980 | |
▼a 201812
▼f 2019 |
| 990 | |
▼a 관리자 |