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Peptide Therapeutics and Diagnostics...

Faucher, Franco Fernando,

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Peptide Therapeutics and Diagnostics for Cancer Therapy and Imaging /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Peptide Therapeutics and Diagnostics for Cancer Therapy and Imaging // Franco Fernando Faucher.
Author:	Faucher, Franco Fernando,
Description:	1 electronic resource (441 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
Contained By:	Dissertations Abstracts International86-05B.
Subject:	Infections. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31643297
ISBN:	9798346382188

Peptide Therapeutics and Diagnostics for Cancer Therapy and Imaging /
Faucher, Franco Fernando,

Peptide Therapeutics and Diagnostics for Cancer Therapy and Imaging /Franco Fernando Faucher. - 1 electronic resource (441 pages)

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

Peptides 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.

English

ISBN: 9798346382188Subjects--Topical Terms:

1621997
Infections.

Peptide Therapeutics and Diagnostics for Cancer Therapy and Imaging /
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520 $a Peptides 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.
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