Professor of Chemistry
The Scripps Research Institute
Synthesis and Screening of Libraries of Conformationally Constrained, Peptoid-Inspired Oligomers
There is great interest in developing probe molecules and drug leads that target the so-called "undruggable proteome." This is perhaps better described as proteins that lack deep molecular crevices that can be targeted with "Rule of Five" small molecules.
It is generally acknowledged that addressing difficult targets, such as those that function via protein-protein interactions, PPIs, will require larger molecules capable of making multiple interactions with the shallow pockets on these proteins. Several laboratories have made significant advances developing PPI inhibitors by structure-guided design of molecules that mimic specific secondary structures in binding partners, such as a-helices.
We have embarked on a different approach in which we attempt to create large libraries of conformationally constrained molecules representing many different "folds." This presentation will cover recent developments in these efforts with a focus on new chemistry and screening strategies.