Exo-chirality of the α-helix

Abstract

The structure of helical polymers is dictated by the molecular chirality of their monomer units. Particularly, macromolecular helices with monomer sequence control have the potential to generate chiral topologies. In α-helical folded peptides, the sequential repetition of amino acids generates a chiral layer defined by the amino acid side chains projected outside the amide backbone. Despite being closely related to peptides’ structural and functional properties, to the best of our knowledge, a general exo-helical symmetry model has not been yet described for the α-helix. Here, we perform the theoretical, computational, and spectroscopic elucidation of the α-helix principal exo-helical topologies. Non-canonical labeled amino acids are employed to spectroscopically characterize the different exo-helical topologies in solution, which precisely match the theorical prediction. Backbone-to-chromophore distance also shows the expected impact in the exo-helices’ geometry and spectroscopic fingerprint. Theoretical prediction and spectroscopic validation of this exo-helical topological model provides robust experimental evidence of the chiral potential on the surface of helical peptides and outlines an entirely new structural scenario for the α-helix. In α-helical folded peptides, the sequential repetition of amino acids generates a chiral layer defined by the amino acid side chains projected outside the amide backbone, and a general exo-helical symmetry model has not been described for the α-helix. Here, the authors introduce the exo-helical symmetry model of the α-helix that results from sequential repetition of amino acid residues and validate the topologies by computational methods and circular dichroism.

Topics & Concepts