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Utilizing Chemoproteomics to Discove...

Berdan, Charles A.

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Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products./
Author:	Berdan, Charles A.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	148 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Contained By:	Dissertations Abstracts International81-03B.
Subject:	Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13861428
ISBN:	9781085781145

Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products.
Berdan, Charles A.

Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 148 p.

Source: Dissertations Abstracts International, Volume: 81-03, Section: B.

Thesis (Ph.D.)--University of California, Berkeley, 2019.

This item must not be sold to any third party vendors.

It is estimated that over 1.7 million people will be diagnosed with cancer and 600,000 people will die from cancer in 2019. The need for new therapeutics against cancer is therefore imperative. Natural product based drug discovery has provided a multitude of effective answers to many diseases, however difficulties in synthesizing natural products, isolating them, and deciphering their mechanism of action can limit translating more natural products into the clinic. Coupling natural product based drug discovery with chemical genetics and with powerful chemoproteomic strategies can allow for new questions to be asked and potentially new therapeutics to be developed even from formerly well-characterized molecules.Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Herein, we further study parthenolide mechanism of action using activity-based protein profiling (ABPP)-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 (C427) of focal adhesion kinase 1 (FAK1) leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a novel functional target exploited by members of a large family of anticancer natural products.

ISBN: 9781085781145Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

Drug discovery

Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products.
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245 1 0 $a Utilizing Chemoproteomics to Discover Novel Druggable Hotspots Targeted by Natural Products.
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500 $a Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
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506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a It is estimated that over 1.7 million people will be diagnosed with cancer and 600,000 people will die from cancer in 2019. The need for new therapeutics against cancer is therefore imperative. Natural product based drug discovery has provided a multitude of effective answers to many diseases, however difficulties in synthesizing natural products, isolating them, and deciphering their mechanism of action can limit translating more natural products into the clinic. Coupling natural product based drug discovery with chemical genetics and with powerful chemoproteomic strategies can allow for new questions to be asked and potentially new therapeutics to be developed even from formerly well-characterized molecules.Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Herein, we further study parthenolide mechanism of action using activity-based protein profiling (ABPP)-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 (C427) of focal adhesion kinase 1 (FAK1) leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a novel functional target exploited by members of a large family of anticancer natural products.
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