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Updated: Sep 16, 2026

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Published on: December 1, 2020
Discovery of High-Affinity Peptide Ligands Targeting the SPIN1 Tudor 3 Domain Via a Minimalist Pruning Strategy
Alessandra Feoli1,2,3,4,5,6, Giulio Esposito1,2,3,4,5,6, Manuela Grimaldi1,2,3,4,5,6
1‡Department of Pharmacy and ∫PhD Program in Drug Discovery and Development, University of Salerno, via Giovanni Paolo II 132, I-84084 Fisciano, SA, Italy.
Abstract:
Spindlin1 (SPIN1) is an epigenetic reader involved in oncology, whose third Tudor domain remains largely underexplored. Here, we applied a minimalist pruning strategy to the 26-mer peptide DOCpep3 to identify the core pharmacophore for SPIN1 Tudor 3 domain binding. This yielded truncated linear peptide analogues (e.g., 1, 3, and 4) displaying low nanomolar affinities, significantly outperforming the parent peptide. Orthogonal biophysical validation (MST and SPR) confirmed competitive target engagement. Furthermore, circular dichroism spectroscopy revealed that these pruned ligands induce distinct structural rearrangements in SPIN1, establishing high-affinity chemical probes for drug discovery.
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