Project Details
Projekt
Pharmacophore-Based Analysis of Multi-Target Natural Compounds for Modulating Lipid Metabolism to Fight Obesity
Applicant
Dr. Anna Lena Wölke
Subject Area
Bioinformatics and Theoretical Biology
Term
from 2015 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 280023142
The aim of the proposed project is to explain the mode-of-action of natural compounds targeting multiple proteins of lipid metabolism to fight obesity. The traditional strategy in drug design is to select one target protein and identify a ligand with high affinity and selectivity. Multi-target drug design in contrast, selects for a ligand that modifies several key proteins moderately in the network disturbed by disease. This moderate multi-target modulation is less vulnerable to bypassing of targets and may cause less severe side effects. Especially the treatment of complex diseases, like cancer, chronic inflammation or obesity, may likely be improved by multi-target drugs. Natural products are well-suited candidates for multi-target drugs being in use in traditional medicine already.In the proposed project, multi-target natural compounds for anti-obesity treatment will be identified and analyzed. 3D-pharmacophore models will be built based on known ligands and protein crystal structures. A pharmacophore is the localization of chemical features in three-dimensional space required for ligand-binding. Databases will be screened for multi-target natural compounds using the pharmacophore models. Most promising hits will be experimentally validated with enzyme-activity and cell-based assays. Based on experimental data, the target list of the compounds will be extended to understand their complete mode-of-action on the system.
DFG Programme
Research Fellowships
International Connection
United Kingdom
