Synthesis and Self-Assembly of Bundle-Forming α-Helical Peptide-Dendron Hybrids

Dendronized helix bundle assemblies combine the sequence diversity and folding properties of proteins with the tailored physical properties of dendrimers. Assembly of peptide-dendron hybrids into alpha-helical bundles encapsulates the helix bundle motif in a dendritic sheath that will allow the functional, protein-like domain to be transplanted to non-biological environments. A bioorthogonal graft-to synthetic strategy for preparing helix bundle-forming peptide-dendron hybrids is described herein for hybrids la, 1b, and 2. Titration experiments monitored by circular dichroism spectroscopy support our self-assembly model for how the peptide-dendron hybrids self-assemble into alpha-helical bundles with the dendrons on outside of the bundle.