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Designing peptide inhibitor of insulin receptor to induce diabetes mellitus type 2 in animal model Mus musculus
Institution:1. Laboratory of Interfaces and Nanosize Systems, Institute of Chemistry, Eötvös Loránd University, Pázmány P. Stny 1/A, H-1117 Budapest, Hungary;2. MTA-BME Research Group of Technical Analytical Chemistry, Szt. Gellért tér 4, H-1111 Budapest, Hungary;3. Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt. Gellért tér 4, H-1111 Budapest, Hungary;4. EKF Department of Chemistry, Leányka u. 6, H-3300 Eger, Hungary;1. Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital - Radium Hospital, Montebello, 0379 Oslo, Norway;2. Division of Orthopaedic Surgery, Oslo University Hospital, Montebello, 0379 Oslo, Norway;3. Department of Immunology, Medical University of Warsaw, 1A Banacha Str, F building, 02-097 Warsaw, Poland
Abstract:A designing peptide as agent for inducing diabetes mellitus type 2 (T2DM) in an animal model is challenging. The computational approach provides a sophisticated tool to design a functional peptide that may block the insulin receptor activity. The peptide that able to inhibit the binding between insulin and insulin receptor is a warrant for inducing T2DM. Therefore, we designed a potential peptide inhibitor of insulin receptor as an agent to generate T2DM animal model by bioinformatics approach. The peptide has been developed based on the structure of insulin receptor binding site of insulin and then modified it to obtain the best properties of half life, hydrophobicity, antigenicity, and stability binding into insulin receptor. The results showed that the modified peptide has characteristics 100 h half-life, high-affinity −95.1 ± 20, and high stability 28.17 in complex with the insulin receptor. Moreover, the modified peptide has molecular weight 4420.8 g/Mol and has no antigenic regions. Based on the molecular dynamic simulation, the complex of modified peptide-insulin receptor is more stable than the commercial insulin receptor blocker. This study suggested that the modified peptide has the promising performance to block the insulin receptor activity that potentially induce diabetes mellitus type 2 in mice.
Keywords:Design  Diabetes mellitus type 2  Insulin receptor  Peptide inhibitor  Modification
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