Supramolecular Peptide Nanostructures Regulate Catalytic Efficiency and Selectivity

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dc.contributor.authorLi, Zhaoen
dc.contributor.authorJoshi, Soumil Y.en
dc.contributor.authorWang, Yinen
dc.contributor.authorDeshmukh, Sanket A.en
dc.contributor.authorMatson, John B.en
dc.date.accessioned2023-06-29T15:15:10Zen
dc.date.available2023-06-29T15:15:10Zen
dc.date.issued2023-05en
dc.description.abstractWe report three constitutionally isomeric tetrapeptides, each comprising one glutamic acid (E) residue, one histidine (H) residue, and two lysine (K-S) residues functionalized with side-chain hydrophobic S-aroylthiooxime (SATO) groups. Depending on the order of amino acids, these amphiphilic peptides self-assembled in aqueous solution into different nanostructures:nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils. Each nanostructure catalyzed hydrolysis of a model substrate, with the nanocoils exhibiting the greatest rate enhancement and the highest enzymatic efficiency. Coarse-grained molecular dynamics simulations, analyzed with unsupervised machine learning, revealed clusters of H residues in hydrophobic pockets along the outer edge of the nanocoils, providing insight for the observed catalytic rate enhancement. Finally, all three supramolecular nanostructures catalyzed hydrolysis of the l-substrate only when a pair of enantiomeric Boc-l/d-Phe-ONp substrates were tested. This study highlights how subtle molecular-level changes can influence supramolecular nanostructures, and ultimately affect catalytic efficiency.en
dc.description.notesAcknowledgments This work was supported by the National Institutes of Health (R01GM123508). We thank Dr. Yulia Shmidov and Prof. Ronit Bitton (Ben Gurion University), and Dr. Einat Nativ-Rot from the electron microscopy unit at the Ilse Katz Institute for Nanoscale Science and Technology at Ben Gurion University for cryo-TEM images. We appreciate experimental support from Dr. Moli Liu and Levena Biopharma in Sorrento Therapeutics Inc. We also acknowledge Prof. Rich Gandour and Prof. Jim Tanko (Virginia Tech) for helpful discussions and suggestions on experimental design and data interpretation, Dr. Santu Sarkar, Dr. Rajnish Kumar, Dr. Sarah Blosch, Sarah Swilley-Sanchez, Dr. Yumeng Zhu, and Abby Chinn for careful readings of the manuscript. The authors also acknowledge use of facilities within the Nanoscale Characterization and Fabrication Laboratory at Virginia Tech.en
dc.description.sponsorshipNational Institutes of Health [R01GM123508]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1002/anie.202303755en
dc.identifier.eissn1521-3773en
dc.identifier.issn1433-7851en
dc.identifier.pmid37194941en
dc.identifier.urihttp://hdl.handle.net/10919/115580en
dc.language.isoenen
dc.publisherWiley-V C Hen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectConstitutional Isomersen
dc.subjectEnantioselectivityen
dc.subjectPeptidesen
dc.subjectSelf-Assemblyen
dc.subjectSimulationen
dc.titleSupramolecular Peptide Nanostructures Regulate Catalytic Efficiency and Selectivityen
dc.title.serialAngewandte Chemie-International Editionen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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