Event Title

Identification of Novel Pepsin Inhibitors for Target Drugs to Treat Laryngopharyngeal Reflux Disease

Presenter Information

Jonathon Gould

Mentor 1

Alexander Arnold

Location

Union 260

Start Date

27-4-2018 12:00 PM

Description

Laryngopharyngeal Reflux Disease (LPRD), an extension of gastroesophageal reflux disease (GERD) occurs when gastric contents are refluxed past the esophagus into the larynx, pharynx, and even the middle ear. Current acid suppression therapy with proton pump inhibitors (PPIs) has proven ineffective because unlike GERD, pepsin is the mechanism behind damaging healthy tissues, not stomach acid. Pepsin is a protease that is produced in the stomach, breaks down larger proteins to smaller peptides and when refluxed extraesophageally can actively digest healthy tissues, damage cells and lead to mutations and subsequent cancers. Herein, we present the synthesis of four novel molecules that were designed by molecular docking using the crystal structure of pepsin to inhibit the enzymatic activity of pepsin. Unfortunately, these compounds were unable to reduce the protolytic activity of pepsin determined by a two independent binding assays. In the future, we will continue to design new reversible inhibitors for pepsin to develop a first-in-class therapy for LPRD.

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Apr 27th, 12:00 PM

Identification of Novel Pepsin Inhibitors for Target Drugs to Treat Laryngopharyngeal Reflux Disease

Union 260

Laryngopharyngeal Reflux Disease (LPRD), an extension of gastroesophageal reflux disease (GERD) occurs when gastric contents are refluxed past the esophagus into the larynx, pharynx, and even the middle ear. Current acid suppression therapy with proton pump inhibitors (PPIs) has proven ineffective because unlike GERD, pepsin is the mechanism behind damaging healthy tissues, not stomach acid. Pepsin is a protease that is produced in the stomach, breaks down larger proteins to smaller peptides and when refluxed extraesophageally can actively digest healthy tissues, damage cells and lead to mutations and subsequent cancers. Herein, we present the synthesis of four novel molecules that were designed by molecular docking using the crystal structure of pepsin to inhibit the enzymatic activity of pepsin. Unfortunately, these compounds were unable to reduce the protolytic activity of pepsin determined by a two independent binding assays. In the future, we will continue to design new reversible inhibitors for pepsin to develop a first-in-class therapy for LPRD.