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Updated: Apr 16, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Tetrahydropyranyl, a nonaromatic acid-labile Cys protecting group for Fmoc peptide chemistry
Iván Ramos-Tomillero1,2, Hortensia Rodríguez1,3, Fernando Albericio1,2,3,4,5
1†Institute for Research in Biomedicine, 08028 Barcelona, Spain.
Abstract:
Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal nonaromatic protecting group for cysteine, has been shown to be superior to Trt, Dpm, Acm, and StBu in solid-phase peptide synthesis using the Fmoc/tBu strategy. Thus, Cys racemization and C-terminal 3-(1-piperidinyl)alanine formation were minimized when the Cys was protected with Thp. This nonaromatic protecting group also improved the solubility of Cys-containing protected peptides.
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