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April 17, 2026Journal of Medicinal Chemistry

Leveraging Diverse Bi-Triazine Cross-linkers for Modulating Conformation and Biological Activity of Cyclic and Dimeric Peptides

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Authors

QZQuan ZuoXYXimiao YangJLJunlong Lu

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Overview

This investigation uncovers how bi-triazine cross-linkers influence peptide conformation and biological activity, suggesting pathways for therapeutic advancements.

Key Points

  • The aim is to link cross-linker geometry with peptide conformation and biological performance.
  • Utilized eight bi-triazine cross-linkers with varying geometries
  • Studied cyclic RGD and dimeric KTLLPTP peptides as models
  • Conducted binding assays and cellular studies
  • Employed in vivo Ga-PET/CT imaging for evaluation
  • Identified lead candidate [68Ga]Ga-8a with ∼5 %ID/mL tumor contrast
  • In cyclic peptides, aromaticity and symmetry were crucial for binding
  • For dimeric peptides, bond length and angle improved binding via the 'molecular ruler' effect

Cite This Study

Zuo et al. (2026) studied this question.

synapsesocial.com/papers/69e1ce3b5cdc762e9d857470https://doi.org/10.1021/acs.jmedchem.6c00693
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