Molecular features characterizing non-peptide selectivity to the human B1 and B2 bradykinin receptors.

Molecular features characterizing non-peptide selectivity to the human B1 and B2 bradykinin receptors. Bioorg Med Chem Lett. 2018 Nov 14;: Authors: Rasaeifar B, Lupala CS, Gomez-Gutierrez P, Perez JJ Abstract Bradykinin is produced in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases. Actions of this peptide are mediated through two different G-protein coupled receptors, named B1 and B2 that have different pharmacological characteristics. The former is up-regulated during inflammation episodes or tissue trauma whereas, the latter is constitutively expressed in a variety of cell types. In a previous work we have characterized the molecular features that explain the observed structure-activity results for both receptors by means of molecular modeling studies, using diverse ligands for both receptors. These results were summarized in the form of two different pharmacophores that provided new insights to be used for the design of novel molecules with antagonistic profile. In the present work, we compare these pharmacophores to understand the features that characterize ligand selectivity to the two bradykinin receptors. The study shows that most of the residues involved in the binding pocket are similar in both receptors and consequently are the pharmacophores obtained. The main difference between the two pharmacophores remains on point #5 that involves a polar moiety for the B1 receptor and an aroma...
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Tags: Bioorg Med Chem Lett Source Type: research