Affiliation:
1. Department of Organic Chemistry Indian Institute of Science Bengaluru 560012 India
2. CSIR-Central Drug Research Institute Lucknow 226031 India
3. School of Life Sciences Central University of Rajasthan Bandar Sindri Ajmer 305817 Rajasthan India
Abstract
AbstractThe 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.