Simulation of binding of deoxyglucose derivatives with glucose transporter Design new drugs for tumor targeting

計畫名稱:Simulation of binding of deoxyglucose derivatives with glucose transporter Design new drugs for tumor targeting

所屬單位:生技所

研究團隊:幹細胞與再生醫學實驗室

計畫主持人:李宣書

研究人員:王美惠

資源需求:Discovery studio

使用期間:2015/02~

研究主題:
Simulation of binding of deoxyglucose derivatives with glucose transporter Design new drugs for tumor targeting

研究內容概述:
We are doing some molecular imaging agents for liver carcinoma targeting. We have synthesized some NDG and ODG compounds, and have applied these compounds onto the liver cancer mice models. The target is glucose transporter. FDG is used as the positive control to see if the glucose transporter can bind with FDG well. The result is satisfying by lib-dock. NDG and ODG are derivatives of FDG, and we are wondering if they can bind with glucose transporter as well, so we would like to use the DS function. However, their molecular weights are more than 3000, so it is not suitable to use Lib-Dock for this purpose. Structure-Based Design and the related Fragment-Based Design are well established strategies in the rational development of small molecule drugs. Knowledge of how a small molecule binds into a protein affords considerable advantages, both in terms of prioritizing compounds for early stage screening, through to optimizing potency and selectivity. DS delivers a comprehensive, scalable portfolio of scientific tools, tailored to support and assist SBD and FBD strategies from hit discovery through to late-stage lead optimization. Prepare macromolecule structures for SBD, analyze and prepare 3D structure models using MODELER. Predict residue ionization states at pH Identify and study putative ligand binding sites. Perform virtual screening on ligands and fragments using either the CATALYST pharmacophore engine, or the Lib-Dock or CDOCKER docking approaches.

We hope to try other programs in the DS software. We have done some animal studies, and have found the biological results. We would like to investigate the structure effects on the binding with glucose transporter by computer simulation and molecular imaging techniques. If the results of simulation and biological imaging data are consistent, it is possible for us to use this computer simulation platform to predict the possible targeting molecule. In addition, the behaviors are not the same between NDG and ODG. We hope DS can give us some possible reason to find the key residues for the tumor targeting.

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