Negating coordinative cysteine and methionine residues during metathesis of unprotected peptides.
Amy L ThomsonEllen C GleesonAlessia BelgiW Roy JacksonEkaterina I IzgorodinaAndrea J RobinsonPublished in: Chemical communications (Cambridge, England) (2023)
Ru-Alkylidene catalysed olefin metathesis generates metabolically stable cystine bridge peptidomimetics with defined geometry. Deleterious coordinative bonding to the catalyst by sulfur-containing functionality found in cysteine and methionine residues can be negated by in situ and reversible oxidation of thiol and thioether functionality, as disulfides and S-oxides respectively, to facilitate high yielding ring-closing and cross metathesis of bioorthogonally protected peptides.