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Updated: Sep 7, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Kinetic and Thermodynamic Control of Macrocyclic Peptide Conformation through Late-Stage Chemical Modification
Yang Daniel Ou1, Joonseong Hur1,2, Chloe Baloh1
1Department of Chemistry, University of Toronto, 80 St. George St, Toronto, OntarioM5S 3H6, Canada.
Abstract:
We describe the use of lactone ring-opening as a chemical tool for producing differentiated conformations of macrocyclic peptides. Under kinetic control, the lactone opening is highly atroposelective across macrocyclic precursors tested. Under thermodynamic control, reversible lactone opening equilibrates the atropisomers. A combined NMR/molecular dynamics study reveals that the atropisomers arising from lactone opening can adopt markedly different conformations, ranging from a 310-helix to various noncanonical conformations. In the RGD-containing macrocycle, the kinetic atropisomer recapitulates the 3D geometry involved in integrin binding, whereas the thermodynamic atropisomer adopts a distinct conformation that was not previously described. Together, these results establish a new strategy to control the conformational states of macrocyclic peptides.
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