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Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr
The novel phenylalanine analogues 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Bcp) and 2',6'-dimethyl-4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Dbcp) were substituted for Tyr(1) in the delta opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH; Tic = tet...
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| Published in: | Journal of medicinal chemistry 2009-11, Vol.52 (21), p.6941-6945 |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 6945 |
| container_issue | 21 |
| container_start_page | 6941 |
| container_title | Journal of medicinal chemistry |
| container_volume | 52 |
| creator | BEREZOWSKA, Irena CHUNG, Nga N LEMIEUX, Carole WILKES, Brian C SCHILLER, Peter W |
| description | The novel phenylalanine analogues 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Bcp) and 2',6'-dimethyl-4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Dbcp) were substituted for Tyr(1) in the delta opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH; Tic = tetrahydroisoquinoline-3-carboxylic acid). Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high delta antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites. The dipeptide H-Dbcp-Tic-OH was a highly selective delta antagonist with subnanomolar delta receptor affinity. |
| doi_str_mv | 10.1021/jm9004913 |
| format | article |
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Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high delta antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites. The dipeptide H-Dbcp-Tic-OH was a highly selective delta antagonist with subnanomolar delta receptor affinity.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm9004913</identifier><identifier>PMID: 19827750</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Binding Sites ; Biological and medical sciences ; Ligands ; Medical sciences ; Models, Molecular ; Molecular Dynamics Simulation ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Oligopeptides - chemical synthesis ; Oligopeptides - chemistry ; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems ; Pharmacology. 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Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high delta antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites. The dipeptide H-Dbcp-Tic-OH was a highly selective delta antagonist with subnanomolar delta receptor affinity.</description><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Molecular Dynamics Simulation</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Oligopeptides - chemical synthesis</subject><subject>Oligopeptides - chemistry</subject><subject>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Conformation</subject><subject>Receptors, Opioid, delta - agonists</subject><subject>Receptors, Opioid, delta - antagonists & inhibitors</subject><subject>Receptors, Opioid, delta - chemistry</subject><subject>Tyrosine - chemistry</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNo90E1OwzAQBWALgaAUFlwAeYNYBeyxEyfLUvEnVbSLsq6mybh1lcQhTiv1XpyDMxFEYTWa0aenp2HsSoo7KUDeb6pMCJ1JdcQGMgYR6VToYzYQAiCCBNQZOw9hI4RQEtQpO5NZCsbEYsCq0crXLnR8F_io7vCwPdAad8633Fv-9cmnjfOu4DNqOldQ4GPfU1e7esXf_I5KPltTvS-xxP5GfRCWfrXtoav5rMScfnLm-_aCnVgsA10e5pC9Pz3Oxy_RZPr8Oh5Noga06KIsy9DmYMgQ2awgEwNmSioyiKiXJl8WlFgrU62s1qnVCZrEiAJUTEkOiRqy29_cpvUffY9uUbmQU9n3I78NC6O0hCQWppfXB7ldVlQsmtZV2O4Xfx_qwc0BYMixtC3WuQv_DkCKFBKpvgHSwHVs</recordid><startdate>20091112</startdate><enddate>20091112</enddate><creator>BEREZOWSKA, Irena</creator><creator>CHUNG, Nga N</creator><creator>LEMIEUX, Carole</creator><creator>WILKES, Brian C</creator><creator>SCHILLER, Peter W</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20091112</creationdate><title>Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr</title><author>BEREZOWSKA, Irena ; CHUNG, Nga N ; LEMIEUX, Carole ; WILKES, Brian C ; SCHILLER, Peter W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p240t-999afc27e7eef9de752a9313e7aaa4b7cbde6ff1843f448f46a7670d235e6c263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Molecular Dynamics Simulation</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Oligopeptides - chemical synthesis</topic><topic>Oligopeptides - chemistry</topic><topic>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Conformation</topic><topic>Receptors, Opioid, delta - agonists</topic><topic>Receptors, Opioid, delta - antagonists & inhibitors</topic><topic>Receptors, Opioid, delta - chemistry</topic><topic>Tyrosine - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BEREZOWSKA, Irena</creatorcontrib><creatorcontrib>CHUNG, Nga N</creatorcontrib><creatorcontrib>LEMIEUX, Carole</creatorcontrib><creatorcontrib>WILKES, Brian C</creatorcontrib><creatorcontrib>SCHILLER, Peter W</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BEREZOWSKA, Irena</au><au>CHUNG, Nga N</au><au>LEMIEUX, Carole</au><au>WILKES, Brian C</au><au>SCHILLER, Peter W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J Med Chem</addtitle><date>2009-11-12</date><risdate>2009</risdate><volume>52</volume><issue>21</issue><spage>6941</spage><epage>6945</epage><pages>6941-6945</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The novel phenylalanine analogues 4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Bcp) and 2',6'-dimethyl-4'-[N-((4'-phenyl)phenethyl)carboxamido]phenylalanine (Dbcp) were substituted for Tyr(1) in the delta opioid antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH; Tic = tetrahydroisoquinoline-3-carboxylic acid). Unexpectedly, [Bcp(1)]TIPP was a potent, selective delta opioid agonist, whereas [Dbcp(1)]TIPP retained high delta antagonist activity. Receptor docking studies indicated similar binding modes for the two peptides except for the biphenylethyl moiety which occupied distinct receptor subsites. The dipeptide H-Dbcp-Tic-OH was a highly selective delta antagonist with subnanomolar delta receptor affinity.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19827750</pmid><doi>10.1021/jm9004913</doi><tpages>5</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 2009-11, Vol.52 (21), p.6941-6945 |
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| language | eng |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Binding Sites Biological and medical sciences Ligands Medical sciences Models, Molecular Molecular Dynamics Simulation Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Oligopeptides - chemical synthesis Oligopeptides - chemistry Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Protein Conformation Receptors, Opioid, delta - agonists Receptors, Opioid, delta - antagonists & inhibitors Receptors, Opioid, delta - chemistry Tyrosine - chemistry |
| title | Agonist vs Antagonist Behavior of δ Opioid Peptides Containing Novel Phenylalanine Analogues in Place of Tyr |
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