title: Metal-Assisted Folding of Prolinomycin Allows Facile Design of Functional Peptides.
abstract: Cyclic peptides have been proposed as privileged scaffolds that might mimic the folding and function of natural proteins. However, simple cyclic peptides typically cannot fold into well-defined structures. Herein, we describe a foldable cyclic peptide scaffold on which functional side chains can be displayed for targeted recognition of biomolecules. The foldable scaffold is based on prolinomycin, a proline-rich analogue of valinomycin. We report synthetic mutants of prolinomycin that retain the metal-assisted folding behavior under physiological conditions. The predictable structure formation of prolinomycin makes it a powerful platform to enable the development of synthetic receptors for biomolecules of interest. We demonstrate the potential of this scaffold by creating prolinomycin mutants that selectively bind anionic vesicles and bacterial cells.
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Azade S
authors.initials: AS
authors.lastname: Hosseini
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Haeffner
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Jianmin
authors.identifier: 0000-0001-9341-1287
authors.initials: J
authors.lastname: Gao
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D015394:Molecular Structure; D009154:Mutation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011189:Potassium Chloride / Q000737:chemistry; D017510:Protein Folding; D011506:Proteins / Q000138:chemical synthesis / Q000235:genetics; D012965:Sodium Chloride / Q000737:chemistry; D014634:Valinomycin / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D010456:Peptides, Cyclic; D011506:Proteins; D014634:Valinomycin; D012965:Sodium Chloride; D011189:Potassium Chloride
keywords: K+ binding; cyclic peptide; peptide design; prolinomycin