Loading…
Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors
Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH ( ), a cyclic peptide with high aff...
Saved in:
Published in: | International journal of molecular sciences 2022-10, Vol.23 (20), p.12700 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3 |
---|---|
cites | cdi_FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3 |
container_end_page | |
container_issue | 20 |
container_start_page | 12700 |
container_title | International journal of molecular sciences |
container_volume | 23 |
creator | Wtorek, Karol Ghidini, Alessia Gentilucci, Luca Adamska-Bartłomiejczyk, Anna Piekielna-Ciesielska, Justyna Ruzza, Chiara Sturaro, Chiara Calò, Girolamo Pieretti, Stefano Kluczyk, Alicja McDonald, John Lambert, David G Janecka, Anna |
description | Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH
(
), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH
, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH
(
) and RP-170-Gly
-RYYRIK-NH
(
). In vitro, the chimeric
gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while
behaved as a mixed MOP/NOP agonist with low nM affinity. Hence,
was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that
administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly
spacer. |
doi_str_mv | 10.3390/ijms232012700 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_819627af45404fe79afa47b69584b618</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_819627af45404fe79afa47b69584b618</doaj_id><sourcerecordid>2728489926</sourcerecordid><originalsourceid>FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3</originalsourceid><addsrcrecordid>eNpdkktv1DAURiMEog9YskWW2LAg4HfsDVIZClQqTAVlbTl-ZDw48dROKs2_J9MpVYeVLd_jo3uvvqp6heB7QiT8ENZ9wQRDhBsIn1THiGJcQ8ibp4_uR9VJKWsIZ5DJ59UR4VgSxshxFX9th3HlSijvwKeQYuqC0RGcmTHchnEL9GDB9xSdmaLO4HMyf8LQgeTBYhV6l4MBV24zBusKuNa5c-OuvNyEFOzd3x_LK_DTmZlJubyonnkdi3t5f55Wv7-cXy--1ZfLrxeLs8vaUIHGmkHqOGwlgZogJLGAvvWEGeaYFr4R0raUcGMRRxJpAxHCWnJhbWsFsjN6Wl3svTbptdrk0Ou8VUkHdfeQcqd0HoOJTgkkOW60p4xC6l0jtde0ablkgrYcidn1ce_aTG3vrHHDmHU8kB5WhrBSXbpVkkM6tz8L3t4LcrqZXBlVH4pxMerBpako3GDJsIScz-ib_9B1mvIwr2pHCSqkxDuq3lMmp1Ky8w_NIKh2mVAHmZj5148neKD_hYD8BUr7skM</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2728489926</pqid></control><display><type>article</type><title>Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Wtorek, Karol ; Ghidini, Alessia ; Gentilucci, Luca ; Adamska-Bartłomiejczyk, Anna ; Piekielna-Ciesielska, Justyna ; Ruzza, Chiara ; Sturaro, Chiara ; Calò, Girolamo ; Pieretti, Stefano ; Kluczyk, Alicja ; McDonald, John ; Lambert, David G ; Janecka, Anna</creator><creatorcontrib>Wtorek, Karol ; Ghidini, Alessia ; Gentilucci, Luca ; Adamska-Bartłomiejczyk, Anna ; Piekielna-Ciesielska, Justyna ; Ruzza, Chiara ; Sturaro, Chiara ; Calò, Girolamo ; Pieretti, Stefano ; Kluczyk, Alicja ; McDonald, John ; Lambert, David G ; Janecka, Anna</creatorcontrib><description>Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH
(
), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH
, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH
(
) and RP-170-Gly
-RYYRIK-NH
(
). In vitro, the chimeric
gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while
behaved as a mixed MOP/NOP agonist with low nM affinity. Hence,
was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that
administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly
spacer.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms232012700</identifier><identifier>PMID: 36293553</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Affinity ; Agonists ; Analgesics ; Analgesics - pharmacology ; Analgesics, Opioid - therapeutic use ; Animals ; antitociceptive test ; Biological activity ; calcium mobilization assay ; Chimera ; Chimeras ; chimeric peptides ; Clinical trials ; Computer applications ; Design ; docking studies ; Dose-Response Relationship, Drug ; Drug dosages ; In vivo methods and tests ; Ligands ; Mice ; Molecular docking ; Molecular Docking Simulation ; Morphine ; Motor task performance ; Naloxone ; Narcotic Antagonists - pharmacology ; Narcotics ; Nociceptin ; nociceptin receptor ; Opioid receptors ; Pain perception ; Peptides ; Peptides - pharmacology ; Peptides, Cyclic ; Receptors, Opioid - agonists ; Receptors, Opioid, kappa ; Receptors, Opioid, mu - agonists ; Sensitivity analysis</subject><ispartof>International journal of molecular sciences, 2022-10, Vol.23 (20), p.12700</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3</citedby><cites>FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3</cites><orcidid>0000-0002-3567-6962 ; 0000-0002-2708-9223 ; 0000-0003-2943-2782 ; 0000-0003-4769-8090 ; 0000-0001-9134-3161 ; 0000-0003-1360-202X ; 0000-0003-1063-7067 ; 0000-0001-5926-6194</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2728489926/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2728489926?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36293553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wtorek, Karol</creatorcontrib><creatorcontrib>Ghidini, Alessia</creatorcontrib><creatorcontrib>Gentilucci, Luca</creatorcontrib><creatorcontrib>Adamska-Bartłomiejczyk, Anna</creatorcontrib><creatorcontrib>Piekielna-Ciesielska, Justyna</creatorcontrib><creatorcontrib>Ruzza, Chiara</creatorcontrib><creatorcontrib>Sturaro, Chiara</creatorcontrib><creatorcontrib>Calò, Girolamo</creatorcontrib><creatorcontrib>Pieretti, Stefano</creatorcontrib><creatorcontrib>Kluczyk, Alicja</creatorcontrib><creatorcontrib>McDonald, John</creatorcontrib><creatorcontrib>Lambert, David G</creatorcontrib><creatorcontrib>Janecka, Anna</creatorcontrib><title>Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH
(
), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH
, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH
(
) and RP-170-Gly
-RYYRIK-NH
(
). In vitro, the chimeric
gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while
behaved as a mixed MOP/NOP agonist with low nM affinity. Hence,
was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that
administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly
spacer.</description><subject>Affinity</subject><subject>Agonists</subject><subject>Analgesics</subject><subject>Analgesics - pharmacology</subject><subject>Analgesics, Opioid - therapeutic use</subject><subject>Animals</subject><subject>antitociceptive test</subject><subject>Biological activity</subject><subject>calcium mobilization assay</subject><subject>Chimera</subject><subject>Chimeras</subject><subject>chimeric peptides</subject><subject>Clinical trials</subject><subject>Computer applications</subject><subject>Design</subject><subject>docking studies</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>In vivo methods and tests</subject><subject>Ligands</subject><subject>Mice</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Morphine</subject><subject>Motor task performance</subject><subject>Naloxone</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Narcotics</subject><subject>Nociceptin</subject><subject>nociceptin receptor</subject><subject>Opioid receptors</subject><subject>Pain perception</subject><subject>Peptides</subject><subject>Peptides - pharmacology</subject><subject>Peptides, Cyclic</subject><subject>Receptors, Opioid - agonists</subject><subject>Receptors, Opioid, kappa</subject><subject>Receptors, Opioid, mu - agonists</subject><subject>Sensitivity analysis</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkktv1DAURiMEog9YskWW2LAg4HfsDVIZClQqTAVlbTl-ZDw48dROKs2_J9MpVYeVLd_jo3uvvqp6heB7QiT8ENZ9wQRDhBsIn1THiGJcQ8ibp4_uR9VJKWsIZ5DJ59UR4VgSxshxFX9th3HlSijvwKeQYuqC0RGcmTHchnEL9GDB9xSdmaLO4HMyf8LQgeTBYhV6l4MBV24zBusKuNa5c-OuvNyEFOzd3x_LK_DTmZlJubyonnkdi3t5f55Wv7-cXy--1ZfLrxeLs8vaUIHGmkHqOGwlgZogJLGAvvWEGeaYFr4R0raUcGMRRxJpAxHCWnJhbWsFsjN6Wl3svTbptdrk0Ou8VUkHdfeQcqd0HoOJTgkkOW60p4xC6l0jtde0ablkgrYcidn1ce_aTG3vrHHDmHU8kB5WhrBSXbpVkkM6tz8L3t4LcrqZXBlVH4pxMerBpako3GDJsIScz-ib_9B1mvIwr2pHCSqkxDuq3lMmp1Ky8w_NIKh2mVAHmZj5148neKD_hYD8BUr7skM</recordid><startdate>20221021</startdate><enddate>20221021</enddate><creator>Wtorek, Karol</creator><creator>Ghidini, Alessia</creator><creator>Gentilucci, Luca</creator><creator>Adamska-Bartłomiejczyk, Anna</creator><creator>Piekielna-Ciesielska, Justyna</creator><creator>Ruzza, Chiara</creator><creator>Sturaro, Chiara</creator><creator>Calò, Girolamo</creator><creator>Pieretti, Stefano</creator><creator>Kluczyk, Alicja</creator><creator>McDonald, John</creator><creator>Lambert, David G</creator><creator>Janecka, Anna</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3567-6962</orcidid><orcidid>https://orcid.org/0000-0002-2708-9223</orcidid><orcidid>https://orcid.org/0000-0003-2943-2782</orcidid><orcidid>https://orcid.org/0000-0003-4769-8090</orcidid><orcidid>https://orcid.org/0000-0001-9134-3161</orcidid><orcidid>https://orcid.org/0000-0003-1360-202X</orcidid><orcidid>https://orcid.org/0000-0003-1063-7067</orcidid><orcidid>https://orcid.org/0000-0001-5926-6194</orcidid></search><sort><creationdate>20221021</creationdate><title>Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors</title><author>Wtorek, Karol ; Ghidini, Alessia ; Gentilucci, Luca ; Adamska-Bartłomiejczyk, Anna ; Piekielna-Ciesielska, Justyna ; Ruzza, Chiara ; Sturaro, Chiara ; Calò, Girolamo ; Pieretti, Stefano ; Kluczyk, Alicja ; McDonald, John ; Lambert, David G ; Janecka, Anna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Affinity</topic><topic>Agonists</topic><topic>Analgesics</topic><topic>Analgesics - pharmacology</topic><topic>Analgesics, Opioid - therapeutic use</topic><topic>Animals</topic><topic>antitociceptive test</topic><topic>Biological activity</topic><topic>calcium mobilization assay</topic><topic>Chimera</topic><topic>Chimeras</topic><topic>chimeric peptides</topic><topic>Clinical trials</topic><topic>Computer applications</topic><topic>Design</topic><topic>docking studies</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug dosages</topic><topic>In vivo methods and tests</topic><topic>Ligands</topic><topic>Mice</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Morphine</topic><topic>Motor task performance</topic><topic>Naloxone</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Narcotics</topic><topic>Nociceptin</topic><topic>nociceptin receptor</topic><topic>Opioid receptors</topic><topic>Pain perception</topic><topic>Peptides</topic><topic>Peptides - pharmacology</topic><topic>Peptides, Cyclic</topic><topic>Receptors, Opioid - agonists</topic><topic>Receptors, Opioid, kappa</topic><topic>Receptors, Opioid, mu - agonists</topic><topic>Sensitivity analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wtorek, Karol</creatorcontrib><creatorcontrib>Ghidini, Alessia</creatorcontrib><creatorcontrib>Gentilucci, Luca</creatorcontrib><creatorcontrib>Adamska-Bartłomiejczyk, Anna</creatorcontrib><creatorcontrib>Piekielna-Ciesielska, Justyna</creatorcontrib><creatorcontrib>Ruzza, Chiara</creatorcontrib><creatorcontrib>Sturaro, Chiara</creatorcontrib><creatorcontrib>Calò, Girolamo</creatorcontrib><creatorcontrib>Pieretti, Stefano</creatorcontrib><creatorcontrib>Kluczyk, Alicja</creatorcontrib><creatorcontrib>McDonald, John</creatorcontrib><creatorcontrib>Lambert, David G</creatorcontrib><creatorcontrib>Janecka, Anna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wtorek, Karol</au><au>Ghidini, Alessia</au><au>Gentilucci, Luca</au><au>Adamska-Bartłomiejczyk, Anna</au><au>Piekielna-Ciesielska, Justyna</au><au>Ruzza, Chiara</au><au>Sturaro, Chiara</au><au>Calò, Girolamo</au><au>Pieretti, Stefano</au><au>Kluczyk, Alicja</au><au>McDonald, John</au><au>Lambert, David G</au><au>Janecka, Anna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2022-10-21</date><risdate>2022</risdate><volume>23</volume><issue>20</issue><spage>12700</spage><pages>12700-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH
(
), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH
, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH
(
) and RP-170-Gly
-RYYRIK-NH
(
). In vitro, the chimeric
gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while
behaved as a mixed MOP/NOP agonist with low nM affinity. Hence,
was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that
administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly
spacer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36293553</pmid><doi>10.3390/ijms232012700</doi><orcidid>https://orcid.org/0000-0002-3567-6962</orcidid><orcidid>https://orcid.org/0000-0002-2708-9223</orcidid><orcidid>https://orcid.org/0000-0003-2943-2782</orcidid><orcidid>https://orcid.org/0000-0003-4769-8090</orcidid><orcidid>https://orcid.org/0000-0001-9134-3161</orcidid><orcidid>https://orcid.org/0000-0003-1360-202X</orcidid><orcidid>https://orcid.org/0000-0003-1063-7067</orcidid><orcidid>https://orcid.org/0000-0001-5926-6194</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1422-0067 |
ispartof | International journal of molecular sciences, 2022-10, Vol.23 (20), p.12700 |
issn | 1422-0067 1661-6596 1422-0067 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_819627af45404fe79afa47b69584b618 |
source | Publicly Available Content (ProQuest); PubMed Central |
subjects | Affinity Agonists Analgesics Analgesics - pharmacology Analgesics, Opioid - therapeutic use Animals antitociceptive test Biological activity calcium mobilization assay Chimera Chimeras chimeric peptides Clinical trials Computer applications Design docking studies Dose-Response Relationship, Drug Drug dosages In vivo methods and tests Ligands Mice Molecular docking Molecular Docking Simulation Morphine Motor task performance Naloxone Narcotic Antagonists - pharmacology Narcotics Nociceptin nociceptin receptor Opioid receptors Pain perception Peptides Peptides - pharmacology Peptides, Cyclic Receptors, Opioid - agonists Receptors, Opioid, kappa Receptors, Opioid, mu - agonists Sensitivity analysis |
title | Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T13%3A16%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis,%20Biological%20Activity%20and%20Molecular%20Docking%20of%20Chimeric%20Peptides%20Targeting%20Opioid%20and%20NOP%20Receptors&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Wtorek,%20Karol&rft.date=2022-10-21&rft.volume=23&rft.issue=20&rft.spage=12700&rft.pages=12700-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms232012700&rft_dat=%3Cproquest_doaj_%3E2728489926%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c481t-504e60b930a3119280fbf35c5e5a8f789db436cd16191ac0112a968ddbd81dbf3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2728489926&rft_id=info:pmid/36293553&rfr_iscdi=true |