Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.

Structural Analysis of Non-native Peptide-Based Catalysts Using 2D NMR-Guided MD Simulations.

Proteins and enzymes generally achieve their functions by creating well-defined 3D architectures that pre-organize reactive functionalities. Mimicking this approach to supramolecular pre-organization is leading to the development of highly versatile artificial chemical environments, including new biomaterials, medicines, artificial enzymes, and enzyme-like catalysts. The use of β-turn and α-helical motifs is one approach that enables the precise placement of reactive functional groups to enable selective substrate activation and reactivity/selectivity that approaches natural enzymes.