Sulfanylmethyldimethylaminopyridine as a Useful Thiol Additive for Ligation Chemistry in Peptide/Protein Synthesis

Kento Ohkawachi; Daishiro Kobayashi; Kyohei Morimoto; Akira Shigenaga; Masaya Denda; Kenzo Yamatsugu; Motomu Kanai; Akira Otaka

doi:10.1021/acs.orglett.0c01383

Sulfanylmethyldimethylaminopyridine as a Useful Thiol Additive for Ligation Chemistry in Peptide/Protein Synthesis

Org Lett. 2020 Jul 17;22(14):5289-5293. doi: 10.1021/acs.orglett.0c01383. Epub 2020 May 12.

Authors

Kento Ohkawachi¹, Daishiro Kobayashi¹, Kyohei Morimoto¹, Akira Shigenaga¹, Masaya Denda¹, Kenzo Yamatsugu², Motomu Kanai², Akira Otaka¹

Affiliations

¹ Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima 770-8505, Japan.
² Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.

PMID: 32396369
DOI: 10.1021/acs.orglett.0c01383

Abstract

Sulfanylmethyl-installed dimethylaminopyridine, 2-sulfanylmethyl-4-dimethylaminopyridine (2), has an acidic thiol group comparable to that in aryl thiols due to the formation of a zwitterion consisting of a thiolate anion and a pyridinium cation. It can be used as an additive for native chemical ligation. The alkyl thiol in 2 allows it to be used for the one-pot native chemical ligation-desulfurization protocol in peptide synthesis. The utility of 2 in the synthesis of cyclic peptides is demonstrated.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkylation
Chemistry Techniques, Synthetic / methods*
Peptides, Cyclic / chemical synthesis*
Peptides, Cyclic / chemistry
Proteins / chemical synthesis*
Proteins / chemistry
Pyridines / chemistry*
Sulfhydryl Compounds / chemistry*

Substances

Peptides, Cyclic
Proteins
Pyridines
Sulfhydryl Compounds
pyridine