Citation: Yunqi Liu, Junliang Zhou, Zhankui Sun. Direct synthesis of unnatural amino acids and modifications of peptides via LADA strategy[J]. Chinese Chemical Letters, ;2024, 35(1): 108553. doi: 10.1016/j.cclet.2023.108553 shu

Direct synthesis of unnatural amino acids and modifications of peptides via LADA strategy

Yunqi Liu ^{a, b, 1} ,
Junliang Zhou ^{a, b, 1} ,
Zhankui Sun ^{a, b, c, d, *,}

a.
Shanghai Frontiers Science Center for Drug Target Identification and Drug Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China
b.
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Pharm-X Center, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China
c.
AI Pharma Center, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China
d.
Shanghai Artificial Intelligence Laboratory, Shanghai 200232, China

zksun@sjtu.edu.cn

Received Date: 4 March 2023
Revised Date: 22 April 2023
Accepted Date: 9 May 2023
Available Online: 10 May 2023

Figures(6)

Unnatural amino acids (UAAs) have broad applications in pharmaceutical sciences and biological studies. Current synthetic methods for UAAs mainly rely on asymmetric catalysis and often require several steps. There is a lack of direct and simple methods. To address this challenge, we designed the LADA (labeling-activation-desulfurization-addition) strategy: selective labeling and activation of cysteine residues, the photocatalytic desulfurization and the subsequent radical addition to alkenes. Although composed of two steps, it is one-pot synthesis and has advantages such as high functional group tolerance, biocompatible reaction condition, and retained stereochemistry. This highly efficient strategy was successfully applied in the direct synthesis of unnatural amino acids and modifications of peptides with more than 50 examples.
- Unnatural amino acids,
- Peptide modifications,
- Desulfurization,
- Cysteine,
- Radical addition
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