Presentation Title

Synthesis and screening of novel polyphenol compounds targeted to inhibit IAPP amyloid aggregation

Start Date

November 2016

End Date

November 2016

Location

HUB 302-#142

Type of Presentation

Poster

Abstract

Aggregation of the pancreatic protein Islet Amyloid Polypeptide (IAPP, amylin) into soluble toxic oligomers and insoluble amyloid appears to play a direct role in the progression of type 2 diabetes. While it remains unclear whether the formation of toxic oligomers and amyloid is a direct cause of this disease or merely a symptom, evidence is mounting that suggests that inhibiting this aggregation may be a key step toward slowing or preventing the progression of this disease. A series of small polyphenol analogs were synthesized based on the structures of known amyloid inhibitors. Treatment of a variety of phenolic acids with tert-butyldimethylsilyl chloride and imidazole followed by hydrolysis of the silyl ester afforded the aryl silyl ethers in good yields. Esterification of several polyols (ethylene glycol, glycerol, and glucose) with protected phenolic acids was achieved using oxalyl chloride and dimethylformamide. Deprotection of the silyl ethers completed the syntheses of the polyphenol analogs in good yields. These compounds were assayed for their ability to inhibit IAPP amyloid formation using standard methods for detecting and quantitating amyloid. Specifically, thioflavin-T binding fluorescence and atomic force microscopy were used to assess the inhibitory potential of the select substances.

This document is currently not available here.

Share

COinS
 
Nov 12th, 4:00 PM Nov 12th, 5:00 PM

Synthesis and screening of novel polyphenol compounds targeted to inhibit IAPP amyloid aggregation

HUB 302-#142

Aggregation of the pancreatic protein Islet Amyloid Polypeptide (IAPP, amylin) into soluble toxic oligomers and insoluble amyloid appears to play a direct role in the progression of type 2 diabetes. While it remains unclear whether the formation of toxic oligomers and amyloid is a direct cause of this disease or merely a symptom, evidence is mounting that suggests that inhibiting this aggregation may be a key step toward slowing or preventing the progression of this disease. A series of small polyphenol analogs were synthesized based on the structures of known amyloid inhibitors. Treatment of a variety of phenolic acids with tert-butyldimethylsilyl chloride and imidazole followed by hydrolysis of the silyl ester afforded the aryl silyl ethers in good yields. Esterification of several polyols (ethylene glycol, glycerol, and glucose) with protected phenolic acids was achieved using oxalyl chloride and dimethylformamide. Deprotection of the silyl ethers completed the syntheses of the polyphenol analogs in good yields. These compounds were assayed for their ability to inhibit IAPP amyloid formation using standard methods for detecting and quantitating amyloid. Specifically, thioflavin-T binding fluorescence and atomic force microscopy were used to assess the inhibitory potential of the select substances.