Beta-Strand Hydrogen Bonds: Contributions to Protein Structure and Optimization for Peptide Drugs

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The 3D arrangements of atoms in complex molecules like proteins determines their function. Those arrangements are dictated largely by noncovalent interactions that remain incompletely understood. We recently discovered a previously overlooked hydrogen bond that is ubiquitous in proteins. These hydrogen bonds occur within individual beta-strands, and we hypothesize that they play key roles in organizing the conformation of complex molecules. In this lecture, I will describe our efforts to quantify these interactions experimentally, which combines approaches from synthetic and physical chemistry. I will also describe a new chemical method we developed to enhance these interactions and how we can exploit this strategy to improve the efficacy of drugs that combat protein misfolding diseases like Alzheimer's and Parkinson's.