The development of peptidomimetic helical foldamers with a wide repertoire of functions is of significant interest. Herein, we report the X-ray crystal structures of a series of homogeneous l-sulfono-γ-AA foldamers and elucidate their folding conformation at the atomic level. Single-crystal X-ray crystallography revealed that this class of oligomers fold into unprecedented dragon-boat-shaped and unexpected left-handed helices, which are stabilized by the 14-hydrogen-bonding pattern present in all sequences. These l-sulfono-γ-AApeptides have a helical pitch of 5.1 Å and exactly four side chains per turn, and the side chains lie perfectly on top of each other along the helical axis. 2D NMR spectroscopy, computational simulations, and CD studies support the folding conformation in solution. Our results provide a structural basis at the atomic level for the design of novel biomimetics with a precise arrangement of functional groups in three dimensions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182766 | PMC |
| http://dx.doi.org/10.1002/anie.201805184 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.
Nat Commun
January 2025
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA.
Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis.
View Article and Find Full Text PDFRNA folding kinetics control riboswitch sensitivity in vivo.
Nat Commun
January 2025
Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL, USA.
Riboswitches are ligand-responsive gene-regulatory RNA elements that perform key roles in maintaining cellular homeostasis. Understanding how riboswitch sensitivity to ligand (EC) is controlled is critical to explain how highly conserved aptamer domains are deployed in a variety of contexts with different sensitivity demands. Here we uncover roles by which RNA folding dynamics control riboswitch sensitivity in cells.
View Article and Find Full Text PDFMethods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.
Protein Sci
February 2025
York Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.
Tryptophan mannosylation, the covalent addition of an α-ᴅ-mannose sugar to a tryptophan side chain, is a post-translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors similar to those seen in N- and O-glycans in the Protein Data Bank (PDB). In this work, we report methods for detecting, building, and improving mannose structures linked to tryptophans.
View Article and Find Full Text PDFRNase P cleavage of pseudoknot substrates reveals differences in active site architecture that depend on residue N-1 in the 5' leader.
RNA Biol
December 2025
Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
We show that a small biotin-binding RNA aptamer that folds into a pseudoknot structure acts as a substrate for bacterial RNase P RNA (RPR) with and without the RNase P C5 protein. Cleavage in the single-stranded region in loop 1 was shown to depend on the presence of a RCCA-motif at the 3' end of the substrate. The nucleobase and the 2'hydroxyl at the position immediately 5' of the cleavage site contribute to both cleavage efficiency and site selection, where C at this position induces significant cleavage at an alternative site, one base upstream of the main cleavage site.
View Article and Find Full Text PDFEngineered initiator tRNAs can effectively start translation at non-AUG start codons and diversify N-terminal amino acids for mRNA Display.
Nucleic Acids Res
January 2025
Department of Peptide Therapeutics, Genentech, South San Francisco, CA 94080, USA.
mRNA display is an effective tool to identify high-affinity macrocyclic binders for challenging protein targets. The success of an mRNA display selection is dependent on generating highly diverse libraries with trillions of peptides. While translation elongation can canonically accommodate the 61 proteinogenic triplet codons, translation initiation is restricted to the native start codon AUG.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!