Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study

Abstract The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immu...

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Main Authors: Molly E. Murray, Beatriz G. Goncalves, Mary A. Biggs, Sophia A. Frantzeskos, Charlotta G. Lebedenko, Ipsita A. Banerjee
Format: Article
Language:English
Published: SpringerOpen 2024-03-01
Series:Applied Biological Chemistry
Subjects:
Online Access:https://doi.org/10.1186/s13765-024-00876-9
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author Molly E. Murray
Beatriz G. Goncalves
Mary A. Biggs
Sophia A. Frantzeskos
Charlotta G. Lebedenko
Ipsita A. Banerjee
author_facet Molly E. Murray
Beatriz G. Goncalves
Mary A. Biggs
Sophia A. Frantzeskos
Charlotta G. Lebedenko
Ipsita A. Banerjee
author_sort Molly E. Murray
collection DOAJ
description Abstract The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immune response and in neurodegenerative diseases. In this work, phytochemical conjugates of two known neuropeptides, melanocyte inhibition factor (MiF-1) and mammalian amidated neuropeptide NPFF with pain modulating ability were developed. The binding interactions of those conjugates with NOP receptor was examined as an approach to develop novel natural compounds that can modulate NOP receptor activity. The selected phytochemicals are well-known for their antioxidant abilities and are derived either from natural alkaloids (betanin), polyphenols (gallic acid and sinapic acid) or terpenes (pomolic acid). Each of the phytochemicals selected are antioxidants which may play a role in mitigating diseases. Three conjugates of betanin were designed with each peptide by conjugating each of the three carboxylic acid groups of betanin with the peptides, while all others were mono-conjugates. Our results indicated that the betanin conjugates with both peptides showed strong binding interactions while the pomolate-peptide conjugates showed moderate binding. In general, NPFF and its conjugates showed stronger binding with the receptor. Docking and molecular dynamics studies revealed that binding interactions occurred at the binding pocket encompassing the transmembrane helices TM1, TM3 and TM7 in most cases, with the ligands binding deep within the hydrophobic core. The binding interactions were further confirmed experimentally through SPR analysis, which also showed higher binding with the betanin conjugates. MMGBSA studies indicated that the binding energies of MiF-1 conjugates were higher compared to neat MiF-1. However, in the case of NPFF, while the betanin conjugates showed enhancement, in some cases the binding energies were found to be slightly reduced compared to neat NPFF. Overall our studies reveal that such natural phytochemical derivatives that can bind to the NOP receptor when conjugated to the mammalian amidated neuropeptide NPFF and the short sequence of melanocyte inhibiting factor MiF-1 may be potentially developed for further laboratory studies for potential pharmaceutical applications.
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spelling doaj.art-75297129c8cd409c91c61a8d500d799f2024-03-10T12:20:30ZengSpringerOpenApplied Biological Chemistry2468-08422024-03-0167112310.1186/s13765-024-00876-9Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR studyMolly E. Murray0Beatriz G. Goncalves1Mary A. Biggs2Sophia A. Frantzeskos3Charlotta G. Lebedenko4Ipsita A. Banerjee5Department of Chemistry and Biochemistry, Fordham UniversityDepartment of Chemistry and Biochemistry, Fordham UniversityDepartment of Chemistry and Biochemistry, Fordham UniversityDepartment of Chemistry and Biochemistry, Fordham UniversityDepartment of Chemistry and Biochemistry, Fordham UniversityDepartment of Chemistry and Biochemistry, Fordham UniversityAbstract The Nociceptin/orphanin FQ peptide (NOP) receptor is considered a member of the opioid receptor subfamily of G-protein coupled receptors (GPCRs) which has been shown to be present in many parts of the central nervous system (CNS). It plays biologically diverse roles in pain modulation, immune response and in neurodegenerative diseases. In this work, phytochemical conjugates of two known neuropeptides, melanocyte inhibition factor (MiF-1) and mammalian amidated neuropeptide NPFF with pain modulating ability were developed. The binding interactions of those conjugates with NOP receptor was examined as an approach to develop novel natural compounds that can modulate NOP receptor activity. The selected phytochemicals are well-known for their antioxidant abilities and are derived either from natural alkaloids (betanin), polyphenols (gallic acid and sinapic acid) or terpenes (pomolic acid). Each of the phytochemicals selected are antioxidants which may play a role in mitigating diseases. Three conjugates of betanin were designed with each peptide by conjugating each of the three carboxylic acid groups of betanin with the peptides, while all others were mono-conjugates. Our results indicated that the betanin conjugates with both peptides showed strong binding interactions while the pomolate-peptide conjugates showed moderate binding. In general, NPFF and its conjugates showed stronger binding with the receptor. Docking and molecular dynamics studies revealed that binding interactions occurred at the binding pocket encompassing the transmembrane helices TM1, TM3 and TM7 in most cases, with the ligands binding deep within the hydrophobic core. The binding interactions were further confirmed experimentally through SPR analysis, which also showed higher binding with the betanin conjugates. MMGBSA studies indicated that the binding energies of MiF-1 conjugates were higher compared to neat MiF-1. However, in the case of NPFF, while the betanin conjugates showed enhancement, in some cases the binding energies were found to be slightly reduced compared to neat NPFF. Overall our studies reveal that such natural phytochemical derivatives that can bind to the NOP receptor when conjugated to the mammalian amidated neuropeptide NPFF and the short sequence of melanocyte inhibiting factor MiF-1 may be potentially developed for further laboratory studies for potential pharmaceutical applications.https://doi.org/10.1186/s13765-024-00876-9Nociceptin/orphanin FQ peptide receptor (NOP) receptorPeptide bindingMelanocyte inhibiting factor-1Molecular dynamics
spellingShingle Molly E. Murray
Beatriz G. Goncalves
Mary A. Biggs
Sophia A. Frantzeskos
Charlotta G. Lebedenko
Ipsita A. Banerjee
Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
Applied Biological Chemistry
Nociceptin/orphanin FQ peptide receptor (NOP) receptor
Peptide binding
Melanocyte inhibiting factor-1
Molecular dynamics
title Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
title_full Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
title_fullStr Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
title_full_unstemmed Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
title_short Exploring the binding interactions of NOP receptor with designed natural phytochemical-neuropeptide conjugates: an in silico and SPR study
title_sort exploring the binding interactions of nop receptor with designed natural phytochemical neuropeptide conjugates an in silico and spr study
topic Nociceptin/orphanin FQ peptide receptor (NOP) receptor
Peptide binding
Melanocyte inhibiting factor-1
Molecular dynamics
url https://doi.org/10.1186/s13765-024-00876-9
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