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Purpose <p>Gout is based on hyperuricaemia and ligands targeting urate are still of interest for therapy. Here we screened a cyclic peptide phage-display library with a urate-derived BSA conjugate (BSA-Com1), obtained clone level evidence that the selected peptides bind a urate-related epitope and tested a small set of leads in a preliminary animal model.</p> Methods <p>An Ala-Cys-X₈-Cys-Gly-Gly-Gly-Ser cyclic peptide library (recombinant positivity 92.5%; capacity &gt; 7.5 × 10⁹) was displayed on M13KE/pIII and screened by three rounds of BSA-Com1 biopanning. Enriched clones were assessed by BSA-Com1/BSA phage ELISA and free-urate competition ELISA. Eight peptides were synthesized; three leads (P1–P3) were tested in adenine-induced hyperuricemic male Sprague-Dawley rats (<i>n</i> = 5/group, baseline serum-urate balanced, intravenous dosing, 7 days).</p> Results <p>Panning returned eight C-X₈-C candidates. Selected clones bound BSA-Com1 above carrier background; soluble urate produced qualitative, clone-level signal changes supportive of epitope engagement. Baseline serum urate was matched across groups (ANOVA <i>P</i> &gt; 0.999). Endpoint serum urate was 144.8 ± 68.1 (model control), 177.6 ± 62.6 (P1), 83.6 ± 34.4 (P2), and 82.0 ± 11.1 µmol/L (P3) (ANOVA <i>P</i> = 0.018). P2 and P3 were significantly lower than P1 (Tukey <i>P</i> = 0.039, 0.035) but did not differ from model controls. H&amp;E and TEM showed no obvious adverse tissue changes.</p> Conclusion <p>BSA-Com1-directed phage display yielded cyclic peptides with qualitative ELISA evidence of urate-epitope engagement. P2 and P3 showed the strongest urate-lowering signals in a small pilot but did not reach significance versus model controls.</p>

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Phage-Display Identification of Urate-Binding Cyclic Peptides with Preliminary Urate-Lowering Activity in Adenine-Induced Hyperuricemic Rats

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Mi Ai,
  • Zhi-Ming Wang,
  • Wei-Lin Guo,
  • Xue-Qi Li,
  • Li-Ting Xiao,
  • Yan-Shan Mai,
  • Hong-Bin Zhang

摘要

Purpose

Gout is based on hyperuricaemia and ligands targeting urate are still of interest for therapy. Here we screened a cyclic peptide phage-display library with a urate-derived BSA conjugate (BSA-Com1), obtained clone level evidence that the selected peptides bind a urate-related epitope and tested a small set of leads in a preliminary animal model.

Methods

An Ala-Cys-X₈-Cys-Gly-Gly-Gly-Ser cyclic peptide library (recombinant positivity 92.5%; capacity > 7.5 × 10⁹) was displayed on M13KE/pIII and screened by three rounds of BSA-Com1 biopanning. Enriched clones were assessed by BSA-Com1/BSA phage ELISA and free-urate competition ELISA. Eight peptides were synthesized; three leads (P1–P3) were tested in adenine-induced hyperuricemic male Sprague-Dawley rats (n = 5/group, baseline serum-urate balanced, intravenous dosing, 7 days).

Results

Panning returned eight C-X₈-C candidates. Selected clones bound BSA-Com1 above carrier background; soluble urate produced qualitative, clone-level signal changes supportive of epitope engagement. Baseline serum urate was matched across groups (ANOVA P > 0.999). Endpoint serum urate was 144.8 ± 68.1 (model control), 177.6 ± 62.6 (P1), 83.6 ± 34.4 (P2), and 82.0 ± 11.1 µmol/L (P3) (ANOVA P = 0.018). P2 and P3 were significantly lower than P1 (Tukey P = 0.039, 0.035) but did not differ from model controls. H&E and TEM showed no obvious adverse tissue changes.

Conclusion

BSA-Com1-directed phage display yielded cyclic peptides with qualitative ELISA evidence of urate-epitope engagement. P2 and P3 showed the strongest urate-lowering signals in a small pilot but did not reach significance versus model controls.