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Stable DNA Motifs, 1D and 2D Nanostructures Constructed from Small Circular DNA Molecules
Published on: April 12, 2019
A Diketone Linchpin Strategy for On-DNA Macrocyclization and Late-Stage Diversification
Qigui Nie1,2,3, Junshan Fan2, Xianfu Fang2,4
1Chongqing University Fuling Hospital, Chongqing University, Chongqing408000, China.
Abstract:
We report a DNA-compatible linchpin strategy for the construction and late-stage diversification of macrocyclic peptide DNA-encoded libraries (MPDELs). Treatment of DNA-conjugated linear peptides with 1,5-dichloropentane-2,4-dione (DPD) enabled highly efficient macrocyclization while introducing a versatile 1,3-diketone linchpin. Subsequent DNA-compatible late-stage diversification afforded four classes of heterocycle-embedded DNA-conjugated macrocycles, including pyrazoles, azolopyrimidines, 2-aminonicotinamides, and 2-hydroxynicotinonitriles, with a broad substrate scope and high conversion. A scale-up test, cross-substrate scope study, and enzymatic ligation demonstrated excellent compatibility with DNA-encoded library synthesis, providing a versatile platform for expanding the chemical space of macrocyclic peptide DNA-encoded libraries.
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