Abstract
The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works by means of different molecular modelling approaches, spreading from homology modelling to manual docking. No small molecules have ever been proposed as agonists of the Ob receptor but researchers’ efforts focused only on leptin-related synthetic peptides as receptor antagonists and on peptidomimetics. In this review we try to track a timeline of obtained in silico information to clarify the mechanism of interaction between leptin and its receptor, together to summarize the more recent efforts to propose new drugs usable in anti-obesity therapy. Final considerations could be useful starting points for the rational drug design of new lead compounds.
Keywords: Homology modelling, leptin, leptin receptor, leptin receptor agonists/antagonists, molecular modelling, protein/protein docking, obesity.
Current Pharmaceutical Design
Title:Leptin and the Ob-Receptor as Anti-Obesity Target: Recent In Silico Advances in the Comprehension of the Protein-Protein Interaction and Rational Drug Design of Anti- Obesity Lead Compounds
Volume: 20 Issue: 1
Author(s): Marco Tutone, Antonino Lauria and Anna Maria Almerico
Affiliation:
Keywords: Homology modelling, leptin, leptin receptor, leptin receptor agonists/antagonists, molecular modelling, protein/protein docking, obesity.
Abstract: The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works by means of different molecular modelling approaches, spreading from homology modelling to manual docking. No small molecules have ever been proposed as agonists of the Ob receptor but researchers’ efforts focused only on leptin-related synthetic peptides as receptor antagonists and on peptidomimetics. In this review we try to track a timeline of obtained in silico information to clarify the mechanism of interaction between leptin and its receptor, together to summarize the more recent efforts to propose new drugs usable in anti-obesity therapy. Final considerations could be useful starting points for the rational drug design of new lead compounds.
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Tutone Marco, Lauria Antonino and Almerico Maria Anna, Leptin and the Ob-Receptor as Anti-Obesity Target: Recent In Silico Advances in the Comprehension of the Protein-Protein Interaction and Rational Drug Design of Anti- Obesity Lead Compounds, Current Pharmaceutical Design 2014; 20 (1) . https://dx.doi.org/10.2174/13816128113196660743
DOI https://dx.doi.org/10.2174/13816128113196660743 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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