Abstract
Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / chemistry
-
Carrier Proteins / antagonists & inhibitors*
-
Cell Adhesion Molecules
-
Cell Adhesion Molecules, Neuronal
-
Cell Line
-
Computer Simulation
-
Drug Design
-
Drug Evaluation, Preclinical
-
Guanylate Kinases
-
Humans
-
Ligands
-
Membrane Proteins / chemistry
-
Models, Molecular
-
Molecular Conformation
-
PTEN Phosphohydrolase / chemistry
-
Phosphoproteins / antagonists & inhibitors
-
Receptors, Drug / drug effects
-
Sodium-Hydrogen Exchangers / antagonists & inhibitors
Substances
-
Adaptor Proteins, Signal Transducing
-
Carrier Proteins
-
Cell Adhesion Molecules
-
Cell Adhesion Molecules, Neuronal
-
Ligands
-
Membrane Proteins
-
PDZK1 protein, human
-
Phosphoproteins
-
Receptors, Drug
-
Sodium-Hydrogen Exchangers
-
sodium-hydrogen exchanger regulatory factor
-
Guanylate Kinases
-
MAGI1 protein, human
-
PTEN Phosphohydrolase