자료유형  

 학위논문

Control Number  

0017160886

International Standard Book Number  

9798382757735

Dewey Decimal Classification Number  

547

Main Entry-Personal Name  

Da Silva, Israel.

Publication, Distribution, etc. (Imprint  

[S.l.] : Northwestern University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

137 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

General Note  

Advisor: Thomson, Regan J.;Kelleher, Neil.

Dissertation Note  

Thesis (Ph.D.)--Northwestern University, 2024.

Summary, Etc.  

요약Natural products and their synthetic analogs have historically been a major contributor for the treatment of disease. Organisms producing these compounds represent a valuable repository, offering intricate structures that inspire the development of potential therapeutics. The rich diversity of natural products also serves as a foundation for the creation of synthetic analogs, propelling innovation in drug discovery and paving the way for novel treatments. This thesis focuses on two different projects involving natural products synthesis and discovery.Advances in mass spectrometry-based metabolomics, bioinformatics, and genetic sequencing capabilities have reinvigorated the field of natural product discovery. Tambromycin, a tetrapeptide with unique structural features, exemplifies the power of combining metabolite data and genomic information through the innovative approach of Metabologenomics. This integrated methodology enhances the precision and efficiency of identifying novel compounds, showcasing the synergy between cutting-edge analytical techniques and genetic insights in uncovering unique natural products. This thesis presents an improved total synthesis approach for trambromycin, resulting in increased material that has helped improve our understanding of its bioactivity profile. The improved synthesis has also played a crucial role in the design and synthesis of tambromycin analogs, offering valuable information into the structure activity relationships within this molecule.The second focal point of this thesis revolves around the targeted discovery of cysteine derived natural products. In contrast to the untargeted method employed in the discovery of tambromycin, which did not emphasize any specific structural features, the targeted approach in this case involves a focused investigation on genes predicted to incorporate cysteine and on metabolites predicted to give a cysteine neutral loss. This strategy aims to enhance the likelihood that the identified natural products have bioactivity. Compounds containing cysteine can undergo transformations leading to a diverse array of functional groups, often regarded as privileged structures. These structures exhibit favorable drug-like properties, enhancing the chances that the discovered natural products are active. By specifically focusing on compounds derived from cysteine, this targeted approach leverages the inherent versatility of cysteine-derived functional groups, contributing to the discovery of potential new therapeutic agents.

Subject Added Entry-Topical Term  

Organic chemistry.

Subject Added Entry-Topical Term  

Biology.

Subject Added Entry-Topical Term  

Chemistry.

Subject Added Entry-Topical Term  

Bioinformatics.

Subject Added Entry-Topical Term  

Genetics.

Index Term-Uncontrolled  

Tambromycin

Index Term-Uncontrolled  

Mass spectrometry

Index Term-Uncontrolled  

Natural products

Index Term-Uncontrolled  

Synthetic chemistry

Index Term-Uncontrolled  

Cysteine

Added Entry-Corporate Name  

Northwestern University Chemistry

Host Item Entry  

Dissertations Abstracts International. 85-11B.

Electronic Location and Access  

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Control Number  

joongbu:656278