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Publication Abstract from PubMed

The rippled beta-sheet is a structural motif formed by certain racemic peptides that is distinct from the commonly known pleated beta-sheet. Although the structure was predicted in 1953, unambiguous crystallographic observation of a rippled beta-sheet was not reported until 2022. The structural foundation of the rippled beta-sheet field continues to expand, stimulating new research questions, both fundamental and applied. Recent studies found that racemic peptides of varied length and amino acid composition assemble into rippled beta-sheets. Intriguingly, certain rippled sheets were found to encapsulate small molecules in ways that could become useful in drug delivery, or to trap harmful substances. These and many other potential applications hinge on the development of a comprehensive structural foundation based on both experiment and theory. In this paper we introduce the concept of the single-component rippled-sheet, composed of joined segments of L and D chirality. The scope of rippled sheet-forming motifs is expanded to include two unexplored classes of rippled sheets: single-component cyclic and linear peptide chimeras. We report on the design, synthesis, and crystal structural characterization of eight self-assembling peptide systems. All five linear systems, in which amino acid sequence, charge and chirality were varied, formed rippled beta-sheets with distinct two- and three-dimensional lattices. Of the three cyclic peptides, however, only one system formed a rippled beta-sheet, while the other two formed pleated beta-sheets. Molecular modeling is used to better understand chiral selection in cyclic systems.

Formation of rippled beta-sheets from mixed chirality linear and cyclic peptides-new structural motifs based on the pauling-corey rippled beta-sheet.,Hazari A, Sawaya MR, Lee H, Sajimon M, Kim H, Goddard Iii WA, Eisenberg D, Raskatov JA Chem Sci. 2025 Mar 6. doi: 10.1039/d4sc08079c. PMID:40060095^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.