Synthesis of a Three-Helix Bundle Protein by Reductive Amination.

An organic trialdehyde, TRIPOD (2), was designed as a template for the synthesis of a three-helix bundle protein. Crystallographic data indicate that the aldehyde groups are appropriately spaced to maximize hydrophobic interactions between the chains of the protein. Peptide strands were attached to the template by reductive amination to yield a bundle protein that is 80% helical at pH 4.1. Synthesis and conformational studies of the bundle protein as well as a model compound are detailed. Binding studies with 1-anilino-8-naphthalenesulfonate, a fluorescent dye, suggest a molten globule state for the bundle protein.