자료유형  

 학위논문

Control Number  

0017164805

International Standard Book Number  

9798346382188

Dewey Decimal Classification Number  

600

Main Entry-Personal Name  

Faucher, Franco Fernando.

Publication, Distribution, etc. (Imprint  

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

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

441 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-05, Section: B.

General Note  

Advisor: Bogyo, Matthew.

Dissertation Note  

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

Summary, Etc.  

요약Peptides have long been part of the drug development pipeline. Therefore, by further exploring the inherent benefits and weaknesses of this modality, we can better design next generation therapeutics and diagnostics. Peptides are generally defined as amino acid polymers comprised of between 2-50 amino acids, making them distinct from small molecules(50 amino acids). Peptides are made of both natural and unnatural amino acid fragments; this modularity has allowed drug designers to generate highly specific therapeutics as many derivatives can be quickly designed to tightly engage the target of interest. Furthermore, the simplicity of their modular design from largely naturally occurring functional groups has allowed drug designers to logically and efficiently modulate properties such as pharmacokinetics, pharmacodynamics, and safety. Due to the natural affinity of peptide like substrates for the active site of proteases, peptides have traditionally been used to target serine hydrolases which play important roles in the pathogenesis of many infectious diseases and cancers. Chapter 1 of this thesis provides a review of recent approaches to use selective covalent inhibitors of serine hydrolases to develop activity-based probes (ABPs). This includes new methodologies that have been designed to improve the potency and specificity of ABPs and to expand their scope and usage as clinically relevant imaging agents. Chapter 2, describes the development of ratiometric activity-based optical contrast agents for image guided surgery. This work addresses many of the current limitations of current clinical contrast agents and demonstrates that peptide-based probes are effective as diagnostic imaging agents. Chapter 3 outlines the use of polymers as scaffolds for improving the in vivoproperties of peptide based imaging contrast agents. These findings provide new insights into the use of polymer-based backbones for enhancing the pharmacodynamic and pharmacokinetic properties of peptide drugs. Chapter 4 outlines a synthesis method for generating diverse covalent cyclic peptides. These peptides are used to identify new druggable targets with the hopes of expanding the druggable proteome. These works, as a collective, are specific applications of peptide-based molecules in the setting of cancer pathologies. Together these works show that peptides can elucidate biological function, such as the case of generating cancer specific fluorescent signals. Furthermore the inhibitor discovery with fluorosulfates shows that peptides can modulate biological systems and can be engineered to create novel functions. Overall, this work provides further evidence for the continued exploration of peptide therapeutics and diagnostics in the context of cancer therapy and imaging.

Subject Added Entry-Topical Term  

Infections.

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Mass spectrometry.

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Neutrophils.

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Binding sites.

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Labeling.

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Design.

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Amino acids.

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Scientific imaging.

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Chemical bonds.

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Fluorides.

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Metabolism.

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Lipids.

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Penicillin.

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Contrast agents.

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Viral infections.

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Pathogenesis.

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Analytical chemistry.

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Medical imaging.

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Pathology.

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Virology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-05B.

Electronic Location and Access  

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Control Number  

joongbu:654303