Citation: Pengxin Wang, Jinyuan Gong, Yuntao Shi, Luping Liu, Rui Wang. Construction-modification method of β-sheet peptides guided by dehydroalanine properties[J]. Chinese Chemical Letters, ;2026, 37(12): 112431. doi: 10.1016/j.cclet.2026.112431 shu

Construction-modification method of β-sheet peptides guided by dehydroalanine properties

Pengxin Wang ^a ,
Jinyuan Gong ^a ,
Yuntao Shi ^a ,
Luping Liu ^{a, *,} ,
Rui Wang ^{a, b, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
b.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, Lanzhou University, Lanzhou 730000, China

lpliu@imm.ac.cn

wangrui@imm.ac.cn

Received Date: 4 November 2025
Revised Date: 5 January 2026
Accepted Date: 18 January 2026
Available Online: 19 January 2026

Figures(4)

Physicochemical properties of amino acids are fundamental to understanding the structure and biological function of peptides, inversely guiding us to control their conformation and function. The construction of conformationally constrained peptides enabled by modification cannot only precisely lock the specific folding structure, but also introduce an additional functional group to enhance their properties and diversify their structures for functional studies. While macrocyclization via various cyclic linkers for the α-helix/cyclic peptides formation has been well established, constructing functionalized β-sheet peptides through modification remains a synthetic challenge. To address this issue, herein we developed a dehydroalanine (Dha)-proline turn template to stabilize β-sheet peptides, in which the Dha-containing turn moiety undergoes a designed double-bond-retained coupling reaction to generate diverse functionalized peptides while maintaining β-sheet integrity. Mechanistic study reveals the unique deprotonation property of Dha under basic conditions and subsequent single-electron transfer (SET) from the enamine moiety of Dha to the diaryliodonium salt.
- Peptide,
- Peptide modification,
- Dehydroalanine,
- β-Sheet,
- Secondary structure
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