title: Using thioamides to site-specifically interrogate the dynamics of hydrogen bond formation in β-sheet folding.
abstract: Thioamides are sterically almost identical to their oxoamide counterparts, but they are weaker hydrogen bond acceptors. Therefore, thioamide amino acids are excellent candidates for perturbing the energetics of backbone-backbone H-bonds in proteins and hence should be useful in elucidating protein folding mechanisms in a site-specific manner. Herein, we validate this approach by applying it to probe the dynamic role of interstrand H-bond formation in the folding kinetics of a well-studied β-hairpin, tryptophan zipper. Our results show that reducing the strength of the peptide's backbone-backbone H-bonds, except the one directly next to the β-turn, does not change the folding rate, suggesting that most native interstrand H-bonds in β-hairpins are formed only after the folding transition state.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Culik
authors.forename: Hyunil
authors.initials: H
authors.lastname: Jo
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
mesh_terms: D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D013854:Thioamides / Q000737:chemistry*; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D013854:Thioamides