ⓘ PK-11195

                                     

ⓘ PK-11195

PK-11195 is an isoquinoline carboxamide which binds selectively to the peripheral benzodiazepine receptor. It is one of the most commonly used PBR ligands due to its high affinity for the PBR in all species, although it is starting to be replaced by newer and more selective ligands.

Autoradiographically early studies using tritium Labeled PK-11195 R-PK11195 binding were detected in patients with stroke, traumatic brain injury and patients with chronic neurodegenerative diseases, including Huntingtons disease and Parkinsons disease.

The first high-resolution 3D solution structure of the mammalian mouse translocator protein tspo in complex with the diagnostic ligand PK11195 was determined using NMR spectroscopy methods, scientists from the Institute. Max Planck for biophysical chemistry in göttingen in Germany in March 2014 and has a pdb-code: 2MGY. The complex Stoichiometry was found to be 1: 1 as one consistent set of ligand 1H resonances was found with the Noe contacts to five transmembrane helices, TM in the upper cytosolic part of the channel protein. Residues involved in binding of ligands has a direct NOE contacts with the ligand were defined as follows A23, version 26, L49, version 26, A50 И52, W107, L114, A147, L150. These residues are wrapped around the PK11195 ligand, forming a stable hydrophobic binding pocket which could also be considered as the hydrophobic core of the complex. In mammalian tspo in complex with the diagnostic ligand is Monomeric.

The loop located between the TM1 and TM2 helices closes the entrance into the space between the spirals which are bound with PK11195 molecule. Site-directed mutagenesis of mtspo studies have shown that region important for PK11195 binding are amino acids from 41 to 51 because deletion of this region resulted in a reduction in PK11195 binding.