Molecular Design Of Conantokin-G Analogues And Their Anti-morphine Dependent Effect In Mice

There are some disadvantages on Con-G, such as the complex chemical synthesis, the high cost and the inconvenient administration disadvantages. in this study, using Homology modeling and Molecular docking, simulating the3D structure of Glu-Con-G and NMDA receptor, retaining the space suitability and binding sites of the complex of Glu-Con-G and NMDA receptor and obtain the essential amino acids (G1, E2, E4, Q6and E10) of Glu-Con-G which interacted with polyamine sites on the ATD of NR1-1a by H-bonds. Based on the H-bonds and energy, the structures of Glu-Con-G, Glu-Con-G[1-11] and Glu-Con-G[S16Y] all conform to docking model. The computer based video tracking CPP system is used to estimate the anti-morphine dependent effects of Glu-Con-G and analogues on the expression of CPP. And Glu-Con-G(240,480pmol)、Glu-Con-G[1-11](480,960pmol) and Glu-Con-G[S16Y](960pmol) decrease the expression of CPP induced by morphine(5mg/kg, i.p.). Glu-Con-G, Glu-Con-G[1-11] and Glu-Con-G[S16Y] can against morphine dependent effect. So this study provides the direction for designing optimized structure of the anti-morphine depandence of conotoxins analogues.