Fmoc-Cys(2,4-hexadiene)-OH is a diene-containing amino acid developed in the Moellering lab for the preparation of Diels-Alder-cyclized peptides for macrocyclization and peptide stabilization. Peptide macrocycles are of increasing interest for improving peptide bioactivity and properties as well as their potential to study, stabilize, or inhibit protein-protein interactions (PPIs).
Journal of the American Chemical Society, 141(41), 16374-16381 (2019-09-17)
Macrocyclization can improve bioactive peptide ligands through preorganization of molecular topology, leading to improvement of pharmacologic properties like binding affinity, cell permeability, and metabolic stability. Here we demonstrate that Diels-Alder [4 + 2] cycloadditions can be harnessed for peptide macrocyclization
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