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Hybrid-Phase Native Chemical Ligation Approaches to Overcome the Limitations of Protein Total Synthesis
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Hybrid-Phase Native Chemical Ligation Approaches to Overcome the Limitations of Protein Total Synthesis. |
| 개인저자 | Yu, Ruixuan Ryan. |
| 단체저자명 | The Ohio State University. Biochemistry Program, Ohio State. |
| 발행사항 | [S.l.]: The Ohio State University., 2016. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2016. |
| 형태사항 | 215 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687937100 |
| 학위논문주기 | Thesis (Ph.D.)--The Ohio State University, 2016. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Ottesen, Jennifer. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Total protein synthesis allows the preparation of proteins with chemically diverse modifications. The numerous advantages of total synthesis are sometimes offset by some major limitations. Protein synthesis is a non-trivial task involving many chemical steps, and these steps increase with the size of the protein. Therefore, larger proteins are difficult to synthesize with high yield. We have developed a strategy which we term hybrid-phase native chemical ligation (NCL) to overcome some of the limitations of size and yield.Hybrid-phase NCL combines ligating peptides on a solid support (solid-phase NCL) and in solution (solution-phase NCL) to maximize synthetic yield. We have successfully used this method to synthesize triple-acetylated histone H4-K5ac,K12ac,K91ac and, for the first time, acetylated centromeric histone CENP-A-K124ac (CpA-K124ac).In order to improve the yield of CENP-A total synthesis, we have incorporated a convergent ligation element in our hybrid-phase strategy. This new approach reduced the number of purification steps, leading to a synthetic yield that was almost triple that of the original approach. Finally, we introduce the convergent solid-phase hybrid NCL approach that allows the preparation of a long peptide segment bearing a masked thioester on a solid support. Through a newly developed resin-anchoring strategy, cleavage of the product from solid-phase generated a ligation-compatible segment that could be used directly with no purification. This method has the potential to synthesize large proteins in good yield, effectively overcoming the size and yield limits of protein total synthesis. |
| 일반주제명 | Chemistry. Biochemistry. Organic chemistry. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
