Improved Stability and Tunable Functionalization of Parallel ?-Sheets via Multicomponent N-Alkylation of the Turn Moiety.

ABSTRACT: In contrast to the myriad of methods available to produce ?-helices and antiparallel ?-sheets in synthetic peptides, just a few are known for the construction of stable, non-cyclic parallel ?-sheets. Herein, we report an efficient on-resin approach for the assembly of parallel ?-sheet peptides in which the N-alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N-alkylated turn using the Ugi reaction on varied isocyano-resins. This four-component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better-structured and more stable parallel ?-sheets in the N-alkylated peptides compared to the non-functionalized variants.

SUBMITTER: Ricardo MG 

PROVIDER: S-EPMC6973259 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature