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Conformation Based in silico Studies of Cyclic Tetrapeptides with βγ Fused Turns as Thrombin Inhibitors

Ghosh, U and Kumar, V and Singh, G and Kanti Chakraborty, T (2023) Conformation Based in silico Studies of Cyclic Tetrapeptides with βγ Fused Turns as Thrombin Inhibitors. In: ChemistrySelect, 8 (11).

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Official URL: https://doi.org/10.1002/slct.202204761


The enormous social and economic consequences of thrombotic diseases, as well as the significant dangers associated with present medications, need the development of more effective and safer anticoagulants. In silico structure-based design was used to find new peptide-based thrombin inhibitors and cyclic peptide-based molecules are attracting wide attention in that regard. Here we have shown the synthesis, conformational and in silico analysis of tetrahydrofuran amino acid (TAA) based 15-membered cyclic tetrapeptides (CTPs) containing guanidine side chain as thrombin inhibitors. Solution NMR conformational analysis suggests that the βγ fused structures of CTPs are retained in the core and there is no effect of guanidine functionality on the scaffold. Molecular docking results showed that these CTPs can inhibit thrombin protein by interacting with Asp189 residue and the core structure helps to retain the guanidine group inside the active site of protein without any alteration in the backbone H-bonding. Overall, we have presented here the synthesis, conformational analysis of TAA containing cyclic tetrapeptides along with their docking study against thrombin protein. Further these results will help to design peptide based novel thrombin inhibitors. © 2023 Wiley-VCH GmbH.

Item Type: Journal Article
Publication: ChemistrySelect
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to John Wiley and Sons Inc.
Keywords: cyclic peptide; guanidine; Tetrahydrofuran amino acid; Thrombin; βγ fused structure
Department/Centre: Division of Chemical Sciences > Organic Chemistry
Date Deposited: 21 Apr 2023 09:44
Last Modified: 21 Apr 2023 09:44
URI: https://eprints.iisc.ac.in/id/eprint/81322

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