(1R,3S)-THCCA-Asn: To show the discovery of selective inhibitor of thrombin by successfully combining virtual screening and biological assay

Zhang, Xiaoyi; Yang, Yifan; Wang, Yuji; Wu, Jianhui; Fang, Qiongyan; Wang, Yaonan; Zhao, Ming; Peng, Shiqi

doi:10.1016/j.ejmech.2022.114681

Cited by 1 publication

(5 citation statements)

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“…Several studies showed the designed or isolated peptides and compounds can be used as thrombin inhibitor. [ 15 , 16 , 23 ] These inhibitors can against human or bovine thrombin. [ 15 , 16 , 23 ] Structural alignment between human [ 34 ] and bovine [ 23 ] thrombin showed they are in high similarity with only 0.229 Å RMSD differences (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…[ 15 , 16 , 23 ] These inhibitors can against human or bovine thrombin. [ 15 , 16 , 23 ] Structural alignment between human [ 34 ] and bovine [ 23 ] thrombin showed they are in high similarity with only 0.229 Å RMSD differences (Fig. 2 A), indicating similar inhibitory mechanism.…”

Section: Resultsmentioning

confidence: 99%

“…The binding pocket of thrombin was determined according to previous studies. [15][16][17]23] Next, we combined the PDB file of the receptor and the ligand for molecular docking. Noticed that the side chain of both protein and peptides were optimized, and peptide conformation was separately refined during docking.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…[12][13][14] Several studies were conducted for screening thrombin inhibitors. [15][16][17] For screening chemical compound inhibitors of thrombin, 16 derivatives of (1R,3S)-2,3,4,9-tetrahydro-βcarboline-3-carboxylic acid with high docking score against bovine thrombin were synthesized and validated their activity. [15] Their results suggested the 16 derivatives can inhibit the platelet aggregation induced by thrombin.…”

Section: Introductionmentioning

confidence: 99%

“…[ 15 – 17 ] For screening chemical compound inhibitors of thrombin, 16 derivatives of (1R,3S)-2,3,4,9-tetrahydro-β-carboline-3-carboxylic acid with high docking score against bovine thrombin were synthesized and validated their activity. [ 15 ] Their results suggested the 16 derivatives can inhibit the platelet aggregation induced by thrombin. In a separate study, Ru et al used soybean protein hydrolyzate to inhibit thrombin.…”

Section: Introductionmentioning

confidence: 99%

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Discovering peptide inhibitors of thrombin as a strategy for anticoagulation

Zhen,

Wang,

et al. 2024

Medicine

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Unusual blood clots can cause serious health problems, such as lung embolism, stroke, and heart attack. Inhibiting thrombin activity was adopted as an effective strategy for preventing blood clots. In this study, we explored computational-based method for designing peptide inhibitors of human thrombin therapeutic peptides to prevent platelet aggregation. The random peptides and their 3-dimentional structures were generated to build a virtual peptide library. The generated peptides were docked into the binding pocket of human thrombin. The designed strong binding peptides were aligned with the native binder by comparative study, and we showed the top 5 peptide binders display strong binding affinity against human thrombin. The 5 peptides were synthesized and validated their inhibitory activity. Our result showed the 5-mer peptide AEGYA, EVVNQ, and FASRW with inhibitory activity against thrombin, range from 0.53 to 4.35 μM. In vitro anti-platelet aggregation assay was carried out, suggesting the 3 peptides can inhibit the platelet aggregation induced by thrombin. This study showed computer-aided peptide inhibitor design can be a robust method for finding potential binders for thrombin, which provided solutions for anticoagulation.

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