Creating synthetic molecules that disrupt protein-protein interactions is difficult because many protein-protein interactions involve the burial of large surface areas (~1500�2). We have begun a project to create bis-peptides � molecules that possess a rigid backbone, exhibit functionality comparable to proteins, and are completely resistant to proteases � that can display large, pre-organized surfaces, which will facilitate protein binding. We are tethering three bis-peptides together utilizing a peptoid backbone to create 'talon' molecules that have a potential interacting surface area of ~2000 �2. These talon molecules can be synthesized in a modular fashion to create combinatorial libraries, which will be used to discover bis-peptide ligands that bind proteins of interest.

Bis-peptide talons as a new set of ligands to bind protein surfaces

244th National Meeting (2012)

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