91桃色

Abstract

Molecular design is a powerful tool that aims to take the most of the structural components of molecules to understand how can they interact and produce the effects that we observe. In our particular case, molecular design has been used to generate new therapeutic agents that help modulate the operation of a specific glutamate receptor and thus prevent negative effects generated by the overstimulation in degenerative processes of the nervous system. For that, we have worked with the ionotropic glutamate receptor type NMDA (NMDAR) which has been previously identified as a pharmaceutical target of importance in degenerative processes of the nervous system in which calcium is a cytotoxic agent for its high influx to the cell. For this work, our target was the GluN2B subunit of NMDA receptor in which interactions with proteins as D2R, DAPK1 and SRC have previously been identified could be involved in calcium excitotoxic processes. We designed and generated some peptides that could specifically inhibit these interactions. We also performed a comparative study of various peptide toxins from marine cones, called conotoxins, to design additional peptides that may interact with GluN2B subunit extracellular domain and get receptor inhibition by this route. By utilizing bioinformatics tools and molecular design, peptides interact with GluN2B subunit of the NMDA receptor and could generate a negative modulation of its operation, allowing the inhibition of the toxic imbalance of calcium in the cell.

Biography

Email: eareyesm@unal.edu.co