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