Well-structured cyclic peptides have been proposed as privileged scaffolds that can mimic the folding and function of natural proteins. Herein we report a novel water-soluble and foldable cyclic peptide scaffold, on which functional side chains can be displayed for targeted recognition of biomolecules. The scaffold derives from prolinomycin, a synthetic K+ transporter. The ion transport is made possible with the K+ induced folding of prolinomycin in lipid membranes. We have synthesized and characterized a series of prolinomycin mutants that harbor polar side chains. The results show that the metal-assisted folding of prolinomycin persists in aqueous media and tolerates various side chain mutations. Grafting proper side chains onto the prolinomycin scaffold allows facile design of peptides that selectively target bacterial membranes. Moreover, the K+ sensitivity of prolinomycin folding can be systematically tuned by incorporating modified proline residues. Overall, the robust folding and tunability makes the prolinomycin scaffold a versatile platform for developing small molecule receptors for biological applications.

Metal-assisted folding of prolinomycin allows facile design of functional peptides

254th National Meeting (2017)

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