Chemical shifts of artificial monomers used to construct heterogeneous‐backbone protein mimetics in random coil and folded states. Issue 2 (12th November 2022)

• Record Type: Journal Article
• Authors: Rao, Shilpa R.; Harmon, Thomas W.; Heath, Shelby L.; Wolfe, Jacob A.; Santhouse, Jacqueline R.; O'Brien, Gregory L.; Distefano, Alexis N.; Reinert, Zachary E.; Horne, W. Seth
• Is Part Of: Peptide science. Volume 115:Issue 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-12
• Subjects: foldamers -- NMR spectroscopy -- peptidomimetics; Peptides -- Periodicals; 572.6505
• DOI: 10.1002/pep2.24297
• Languages: English
• ISSNs: 2475-8817

Abstract

Abstract: The construction of protein‐sized synthetic chains that blend natural amino acids with artificial monomers to create so‐called heterogeneous‐backbones is a powerful approach to generate complex folds and functions from bio‐inspired agents. A variety of techniques from structural biology commonly used to study natural proteins have been adapted to investigate folding in these entities. In NMR characterization of proteins, proton chemical shift is straightforward to acquire and an information‐rich metric that bears directly on a variety of properties related to folding. Leveraging chemical shift to gain insight into folding requires a set of reference chemical shift values corresponding to each building block type (i.e., the 20 canonical amino acids in the case of natural proteins) in a random coil state and knowledge of systematic changes in chemical shift associated with particular folded conformations. Although well documented for natural proteins, these issues remain unexplored in the context of protein mimetics. Here, we report random coil chemical shift values for a library of artificial amino acid monomers frequently used to construct heterogeneous‐backbone protein analogues as well as a spectroscopic signature associated with one monomer class, β 3 ‐residues bearing proteinogenic side chains, adopting a helical folded conformation. Collectively, these results will facilitate the continued utilization of NMR for the study of structure and dynamics in protein‐like artificial backbones. Abstract :