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DOI: 10.1055/a-2536-8969
Design and Synthesis of a C 2-Symmetric Cyclic Decapeptide and Its Peptidomimetic as Potential Inhibitors against Amyloid-β Aggregation
This work was supported in part by grants from the Japan Society for the Promotion of Science (JSPS), KAKENHI [24K02144 (to H.T.) and 23K14318 (to T.K.)], the Japan Agency for Medical Research and Development (AMED) [JP24ama121043 (Research Support Project for Life Science and Drug Discovery, BINDS) (to H.T.)], and the Japan Science and Technology Agency (JST), SPRING [JPMJSP2180 (to K.Y.)].
Abstract
A C 2-symmetric cyclic decapeptide and its peptidomimetic based on the KLVFF fragment of amyloid-β (Aβ) are designed and synthesized as potential inhibitors against Aβ aggregation in Alzheimer’s disease. These compounds are efficiently synthesized using solution- and solid-phase peptide synthesis. Thioflavin-T assays reveal that both the cyclic decapeptide and its chloroalkene dipeptide isostere (CADI)-containing peptidomimetic significantly inhibit Aβ aggregation. These results demonstrate the potential of C 2-symmetric cyclic peptides and peptidomimetics as effective Aβ aggregation inhibitors for Alzheimer’s disease therapies.
Key words
cyclic decapeptide - peptidomimetic - C 2-symmetric - peptide synthesis - Alzheimer’s diseaseSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2536-8969.
- Supporting Information
Publication History
Received: 31 December 2024
Accepted after revision: 10 February 2025
Accepted Manuscript online:
10 February 2025
Article published online:
04 April 2025
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