Title
Screening of Leptin-LepR modulators using molecular docking and binding assay
Authors
Albertana Jiménez-Pineda1, José Luis Vique-Sánchez2, Oscar Medina-Contreras3,* & Claudia G. Benitez-Cardoza1,*
Affiliation
1Laboratorio de Investigación Bioquímica y Biofísica Computacional, ENMyH, Instituto Politécnico Nacional, Guillermo Massieu Helguera, No. 239, Fracc. "La Escalera", Ticomán, C.P. 07320, Ciudad de México, México; 2Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, CP 02100, BC, México; 3Unidad de Investigación Epidemiológica en Endocrinología y Nutrición, Hospital Infantil de México Federico Gómez, CP 06720, Ciudad de México; *Corresponding authors
Albertana Jiménez-Pineda - E-mail: ajimenezp1601@alumno.ipn.mx
José Luis Vique-Sánchez - E-mail: jvique@uabc.edu.mx
Oscar Medina-Contreras - E-mail: omedina@himfg.edu.mx
Claudia G. Benitez-Cardoza - E-mail: cbenitezc@ipn.mx
Article Type
Research Article
Date
Received May 1, 2024; Revised May 31, 2024; Accepted May 31, 2024, Published May 31, 2024
Abstract
Leptin is a pleiotropic hormone which, upon binding to its cognate leptin receptor (LepR), induces the activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades. Hence, we used molecular docking and a chemical library to identify 18 compounds with high probability of interacting with the leptin binding domain (LBD) of LepR. 6 out of 18 compounds were selected based on toxicological and physicochemical properties to evaluate their effect in the formation of Leptin-LepR complex using ELISA assays. The six compounds showed discreet but significant modulation on the complex formation. These results have important implications in proposing novel strategies for modulating the formation of the Leptin-LepR complex, as therapeutic alternatives for patho-physiologies where the formation of this complex is deregulated.
Keywords
Leptin receptor, drug-like compounds, protein-compound docking, interactions, ADMET properties
Citation
Jiménez-Pineda et al. Bioinformation 20(5): 404-411 (2024)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
