Preparation and conformational analysis of polyproline tri-helix macrocycle nanoscaffolds of varied sizes.

Ligand patterns at the nanoscale are essential in modulating biological recognition and signaling through binding to receptor oligomers. Biocompatible nanoscaffolds that allow precise control of multiple ligand presentation would be of great use in manipulating cellular processes and understanding membrane receptor biology. We have previously developed tri-helix and tetra-helix macrocycle scaffolds based on the Pro9 peptide helix to control ligand arrangements that can selectively target receptor oligomers.

Polyproline Tri-Helix Macrocycles as Nanosized Scaffolds to Control Ligand Patterns for Selective Protein Oligomer Interactions.

Multivalent ligand-receptor interactions play essential roles in biological recognition and signaling. As the receptor arrangement on the cell surface can alter the outcome of cell signaling and also provide spatial specificity for ligand binding, controlling the presentation of ligands has become a promising strategy to manipulate or selectively target protein receptors. The lack of adjustable universal tools to control ligand positions at the size of a few nanometers has prompted the development of polyproline tri-helix macrocycles as scaffolds to present ligands in designated patterns.

Controlling Ligand Spacing on Surface: Polyproline-Based Fluorous Microarray as a Tool in Spatial Specificity Analysis and Inhibitor Development for Carbohydrate-Protein Interactions.

Multivalent carbohydrate-protein interactions are essential for many biological processes. Convenient characterization for multivalent binding property of proteins will aid the development of molecules to manipulate these processes. We exploited the polyproline helix II (PPII) structure as molecular scaffolds to adjust the distances between glycan ligand attachment sites at 9, 18, and 27 Å on a peptide scaffold.