Inherent Conformational Preferences of Ac‐Gln‐Gln‐NHBn: Sidechain Hydrogen Bonding Supports a β‐Turn in the Gas Phase. Issue 47 (24th October 2016)

• Record Type: Journal Article
• Authors: Walsh, Patrick S.; Blodgett, Karl N.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 47(2016)
• Page Start: 14618
• Page End: 14622
• Publication Date: 2016-10-24
• Subjects: density functional calculations -- gas-phase chemistry -- glutamine -- IR spectroscopy -- supersonic expansion; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201607842
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Gas‐phase single‐conformation spectroscopy is used to study Ac‐Gln‐Gln‐NHBn in order to probe the interplay between sidechain hydrogen bonding and backbone conformational preferences. This small, amide‐rich peptide offers many possibilities for backbone–backbone, sidechain–backbone, and sidechain–sidechain interactions. The major conformer observed experimentally features a type‐I β‐turn with a canonical 10‐membered ring C=O—H−N hydrogen bond between backbone amide groups. In addition, the C=O group of each Gln sidechain participates in a seven‐membered ring hydrogen bond with the backbone NH of the same residue. Thus, sidechain hydrogen‐bonding potential is satisfied in a manner that is consistent with and stabilizes the β‐turn secondary structure. This turn‐forming propensity may be relevant to pathogenic amyloid formation by polyglutamine segments in human proteins. Abstract : Gas‐phase chemistry : Single‐conformation laser spectroscopy studies of the glutamine‐containing molecule Ac‐Gln‐Gln‐NHBn reveal formation of a type‐I β‐turn in the gas phase. This structure demonstrates the ability of the glutamine sidechain to stabilize this backbone geometry through sidechain‐to‐backbone hydrogen bonds. This structural result is placed in the larger context of polyglutamine neurodegenerative diseases.