Oral Presentation 9th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2023

From Solid-phase Disulfide Ligation to Thioether-mediated Sulfenylation of Tryptophan (96830)

Yoshio Hayashi 1 , Yuma Tokita 1 , Hayate Shida 1 , Yan Cui 1 , Reo Kishi 1 , Sho Konno 1 , Atsuhiko Taniguchi 1 , Akihiro Taguchi 1
  1. Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan

Efficient chemical modification of tryptophan (Trp) is of great interest because Trp and its analogues are widely found in many natural products and biomolecules such as peptides and proteins [1] and are important components for their biological activity. Therefore, the development of a new Trp-selective modification reaction is important in chemical biology and peptide/protein chemistry. To this end, several modifications to the indole ring of Trp using such as organic radical reaction [2] and sulfenylation with S-protected cysteine sulfoxides [3] have already been reported. We have recently developed Npys-OPh(pF), a stable surrogate for Npys-Cl [4,5] with a similar reactivity for modifying the thiol group of Cys and its solid supported form was used for a solid-phase disulfide ligation. Furthermore, we have now found that Npys-OPh(pF) acts as a new sulfenylation reagent for the indole ring of Trp by the activation with thioethers such as Met and diethylsulfide under acidic conditions. This reaction enabled a new selective chemical modification of Trp. The details of the sulfenylation reaction, including its plausible reaction mechanism, will be discussed in this presentation.

  1. Gilis, D., et al., (2001) Genome Biol., 2, research0049.1-0049.12. 2. Seki, Y., et al., (2016) J. Am. Chem. Soc., 138, 10798-10801. 3. Kobayashi, D., et al., (2022) ACS Med. Chem. Lett., 13, 1125-1130. 4. Cui, Y., Hayashi, Y., et al., (2020) Org. Biomol. Chem., 18, 7094-7097. 5. Cui, Y., Hayashi, Y., et al., (2022) Bull. Chem. Soc. Jpn., 95, 1156-1162