title: Tunable control of polyproline helix (PPII) structure via aromatic electronic effects: an electronic switch of polyproline helix.
abstract: Aromatic rings exhibit defined interactions via the unique aromatic π face. Aromatic amino acids interact favorably with proline residues via both the hydrophobic effect and aromatic-proline interactions, C-H/π interactions between the aromatic π face and proline ring C-H bonds. The canonical aromatic amino acids Trp, Tyr, and Phe strongly disfavor a polyproline helix (PPII) when they are present in proline-rich sequences because of the large populations of cis amide bonds induced by favorable aromatic-proline interactions (aromatic-cis-proline and proline-cis-proline-aromatic interactions). We demonstrate the ability to tune polyproline helix conformation and cis-trans isomerism in proline-rich sequences using aromatic electronic effects. Electron-rich aromatic residues strongly disfavor polyproline helix and exhibit large populations of cis amide bonds, while electron-poor aromatic residues exhibit small populations of cis amide bonds and favor polyproline helix. 4-Aminophenylalanine is a pH-dependent electronic switch of polyproline helix, with cis amide bonds favored as the electron-donating amine, but trans amide bonds and polyproline helix preferred as the electron-withdrawing ammonium. Peptides with block proline-aromatic PPXPPXPPXPP sequences exhibited electronically switchable pH-dependent structures. Electron-poor aromatic amino acids provide special capabilities to integrate aromatic residues into polyproline helices and to serve as the basis of aromatic electronic switches to change structure.
authors: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors: Anil K
authors: AK
authors: Pandey
authors: Krista M
authors: KM
authors: Thomas
authors: Christina R
authors: CR
authors: Forbes
authors: Neal J
authors: NJ
authors: Zondlo
mesh_terms: D002942:Circular Dichroism; D007536:Isomerism; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D010455:Peptides; C011083:polyproline