ArticleAngewandte Chemie (International ed. in English)2026
RaPID Selection of Backbone Macrocyclic Peptides Targeting Akt2.
Article in Angewandte Chemie (International ed. in English), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Backbone-cyclic peptides (BMPs) are an attractive class of molecules appeared in diverse natural bioactive products. However, mRNA display technology coupled with ribosomal synthesis is intrinsically inapplicable to such peptide phenotypes due to loss of the C-terminal peptide region linking to the mRNA genotypes. To overcome this issue, we have devised a new strategy to link the sidechain-to-S-mainchain bond via an S-to-N acyl-shift to connect BMPs to the C-terminal fragment of the peptide. Here, we report the application of this strategy to construct a library of BMPs fused to cognate mRNAs. The library was applied for the selection of BMP ligands targeting Akt2, which is involved in the signal pathway to cancer pathogenesis. Consequently, BMP ligands against Akt2 were successfully uncovered from the library. The most potent Akt2 inhibitor, BMPakti-3, showed 1.3 nM of dissociation constant and 34 nM of half-maximal inhibitory concentration (IC
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