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Updated: Aug 5, 2026

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Site-Specific Tyrosine Sulfation of Triabin via Semi-Synthesis Enhances Thrombin Inhibition through Synergistic
Zhenbang Xiao1, Zeyuan Mo1, Litong Lin1
1School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou510640, China.
Abstract:
Herein, we report the semisynthesis of site-specifically sulfated triabin─a 142-amino-acid lipocalin protein─at Tyr124. Functional assays reveal that sulfation enhances anticoagulant activity by ∼5-fold, demonstrating that even rigid scaffolds can benefit from this modification. Modeling studies uncover a synergistic mechanism wherein the sulfate group engages in a hydrogen-bond network, electrostatic bridging, and charge-complementary interactions with thrombin exosite I, while the hydrophobic core (notably Phe106 and Val126) remains the primary driving force.
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