NMR evaluation of interactions between substituted-indole and PDZ1 domain of PSD-95

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 11; pp. 3349 - 3353
• Main Authors: Vogrig, Alexandre, Boucherle, Benjamin, Deokar, Hemantkumar, Thomas, Isabelle, Ripoche, Isabelle, Lian, Lu-Yun, Ducki, Sylvie
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.06.2011; Elsevier
• Subjects: Analgesia; Analgesics; Animals; Biological and medical sciences; chemical derivatives; chemical interactions; Chemical Sciences; Disks Large Homolog 4 Protein; Guanylate Kinases - chemistry; Hydrogen Bonding; indoles; Indoles - chemical synthesis; Indoles - chemistry; Life Sciences; Magnetic Resonance Spectroscopy; Medical sciences; Medication; Medicinal Chemistry; membrane proteins; Membrane Proteins - chemistry; Mice; Models, Molecular; Neuropharmacology; nuclear magnetic resonance spectroscopy; Organic chemistry; PDZ domain; Pharmaceutical sciences; Pharmacology; Pharmacology. Drug treatments; Protein Structure, Tertiary; Protein–protein interaction; PSD-95; Analgesia; PDZ domain; PSD-95; Protein–protein interaction; Protein-protein interaction; Ligand; Molecular interaction; Binding site; NMR spectrometry; Modeling; Biological activity; Protein; Carboxylic acid; Molecular model; Small molecule; Indole derivatives; Chemical synthesis; Molecular domain
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.04.011

We synthesized small organic molecules designed as PDZ ligands. These indole-based compounds were evaluated for their interaction with the PDZ1 domain of the post-synaptic density 95 (PSD-95) protein. Three molecules were found to interact with the targeted PDZ protein by NMR. One of them showed chemical shift perturbations closely related to the natural ligands.