Next Article in Journal
Total Synthesis of Natural Disaccharide Sambubiose
Next Article in Special Issue
Tumor Immunotherapy Using A2A Adenosine Receptor Antagonists
Previous Article in Journal
Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects
Article

New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding

Department of Chemical Engineering, Universitat Politecnica de Catalunya, ETSEIB, Av. Diagonal, 647, 08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(8), 197; https://doi.org/10.3390/ph13080197
Received: 4 August 2020 / Revised: 10 August 2020 / Accepted: 12 August 2020 / Published: 17 August 2020
(This article belongs to the Special Issue GPCRs: Ligands and beyond 2022)
Members of the family of bombesinlike peptides exert a wide range of biological activities both at the central nervous system and in peripheral tissues through at least three G-Protein Coupled Receptors: BB1, BB2 and BB3. Despite the number of peptide ligands already described, only a few small molecule binders have been disclosed so far, hampering a deeper understanding of their pharmacology. In order to have a deeper understanding of the stereochemical features characterizing binding to the BB1 receptor, we performed the molecular modeling study consisting of the construction of a 3D model of the receptor by homology modeling followed by a docking study of the peptoids PD168368 and PD176252 onto it. Analysis of the complexes permitted us to propose prospective bound conformations of the compounds, consistent with the experimental information available. Subsequently, we defined a pharmacophore describing minimal stereochemical requirements for binding to the BB1 receptor that was used in silico screening. This exercise yielded a set of small molecules that were purchased and tested, showing affinity to the BB1 but not to the BB2 receptor. These molecules exhibit scaffolds of diverse chemical families that can be used as a starting point for the development of novel BB1 antagonists. View Full-Text
Keywords: bombesin receptors; neuromedin B antagonism; G-protein coupled receptors homology modeling; non-peptide neuromedin B antagonists bombesin receptors; neuromedin B antagonism; G-protein coupled receptors homology modeling; non-peptide neuromedin B antagonists
Show Figures

Graphical abstract

MDPI and ACS Style

Rasaeifar, B.; Gomez-Gutierrez, P.; Perez, J.J. New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding. Pharmaceuticals 2020, 13, 197. https://doi.org/10.3390/ph13080197

AMA Style

Rasaeifar B, Gomez-Gutierrez P, Perez JJ. New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding. Pharmaceuticals. 2020; 13(8):197. https://doi.org/10.3390/ph13080197

Chicago/Turabian Style

Rasaeifar, Bahareh, Patricia Gomez-Gutierrez, and Juan J. Perez 2020. "New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding" Pharmaceuticals 13, no. 8: 197. https://doi.org/10.3390/ph13080197

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop