Influence of Macrocyclization Strategies on DNA-Encoded Cyclic Peptide Libraries.

ABSTRACT: Discovery of cyclic peptide hits using DNA-encoded libraries (DELs) has recently been extensively researched, with significant efforts directed toward developing DEL-compatible macrocyclization methods. To investigate how different cyclic linkers influence DEL selection outcomes, we constructed eight distinct sublibraries and screened them against two protein targets, MDM2 and GIT1, resulting in two representative yet contrasting scenarios. Validation studies for MDM2 revealed that structural similarity patterns observed across multiple sublibraries could enhance confidence in the authenticity of identified hits. Notably, cmp-10 demonstrated potent inhibitory activity, exhibiting an inhibition constant of 11 nM. In contrast, selections against GIT1 produced discrete enrichment patte

SUBMITTER: Zhao H 

PROVIDER: S-EPMC12308377 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature