Addition of the (28-38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy
Chimeric peptides were synthesized by adding the C‐terminal extension 28‐38 of the pituitary adenylate cyclase activating polypeptide (PACAP) to the sequences (1–27), (2–27), (3–27) and (6–27) of VIP. The capacity of these peptides to occupy the selective PACAP‐ and the non‐selective PACAP‐VIP recep...
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Veröffentlicht in: | International Journal of Peptide and Protein Research 1996-10, Vol.48 (4), p.391-396 |
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description | Chimeric peptides were synthesized by adding the C‐terminal extension 28‐38 of the pituitary adenylate cyclase activating polypeptide (PACAP) to the sequences (1–27), (2–27), (3–27) and (6–27) of VIP. The capacity of these peptides to occupy the selective PACAP‐ and the non‐selective PACAP‐VIP receptors and to stimulate adenylate cyclase activity was studied in Chinese hamster ovary (CHO) cells expressing the recombinant receptors. The results were compared to those obtained with VIP and the corresponding VIP fragments.
The presence of the (28–38) PACAP extension increased at least 100‐fold the VIP‐ or VIP fragment affinities for the selective PACAP receptor but not for the non‐selective PACAP‐VIP receptors. Furthermore, on both receptors, the extension increased peptide intrinsic activity: VIP(3–28) was a partial agonist; while VIP(3–27)/PACAP(28–38) was as potent as VIP and was apparently a full agonist; VIP(6–28) had no intrinsic activity, but VIP(6–27)/PACAP(28–38) was a partial agonist.
These results suggest: (1) the presence of a specific domain for the (28–38) PACAP sequence on the selective PACAP receptor; and (2) a stabilizing effect of the (28–38) PACAP sequence on the structure of N‐terminally truncated VIP. © Munksgaard 1996. |
doi_str_mv | 10.1111/j.1399-3011.1996.tb00856.x |
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The presence of the (28–38) PACAP extension increased at least 100‐fold the VIP‐ or VIP fragment affinities for the selective PACAP receptor but not for the non‐selective PACAP‐VIP receptors. Furthermore, on both receptors, the extension increased peptide intrinsic activity: VIP(3–28) was a partial agonist; while VIP(3–27)/PACAP(28–38) was as potent as VIP and was apparently a full agonist; VIP(6–28) had no intrinsic activity, but VIP(6–27)/PACAP(28–38) was a partial agonist.
These results suggest: (1) the presence of a specific domain for the (28–38) PACAP sequence on the selective PACAP receptor; and (2) a stabilizing effect of the (28–38) PACAP sequence on the structure of N‐terminally truncated VIP. © Munksgaard 1996.</description><identifier>ISSN: 0367-8377</identifier><identifier>EISSN: 1399-3011</identifier><identifier>DOI: 10.1111/j.1399-3011.1996.tb00856.x</identifier><identifier>PMID: 8919060</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adenylyl Cyclases - metabolism ; Amino Acid Sequence ; Animals ; Binding, Competitive ; CHO Cells ; Cricetinae ; Cyclic AMP - biosynthesis ; Dose-Response Relationship, Drug ; Iodine Radioisotopes ; Membranes - metabolism ; Molecular Sequence Data ; Neuropeptides - analysis ; Neuropeptides - chemistry ; Neuropeptides - metabolism ; PACAP ; PACAP receptors ; peptide analogues ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Radioligand Assay ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Pituitary Hormone - metabolism ; Receptors, Vasoactive Intestinal Peptide - metabolism ; Recombinant Fusion Proteins - chemistry ; Recombinant Fusion Proteins - metabolism ; Sensitivity and Specificity ; Vasoactive Intestinal Peptide - analysis ; Vasoactive Intestinal Peptide - chemistry ; Vasoactive Intestinal Peptide - metabolism ; VIP ; VIP receptors</subject><ispartof>International Journal of Peptide and Protein Research, 1996-10, Vol.48 (4), p.391-396</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4741-b464761bed94030eeba2c156c371e5032e070d089997e00a74618d69b73961693</citedby><cites>FETCH-LOGICAL-c4741-b464761bed94030eeba2c156c371e5032e070d089997e00a74618d69b73961693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1399-3011.1996.tb00856.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1399-3011.1996.tb00856.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8919060$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GOURLET, PHILIPPE</creatorcontrib><creatorcontrib>VANDERMEERS, ANDRÉ</creatorcontrib><creatorcontrib>VANDERMEERS-PIRET, MARIE-CLAIRE</creatorcontrib><creatorcontrib>DE NEEF, PHILIPPE</creatorcontrib><creatorcontrib>ROBBERECHT, PATRICK</creatorcontrib><title>Addition of the (28-38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy</title><title>International Journal of Peptide and Protein Research</title><addtitle>Int J Pept Protein Res</addtitle><description>Chimeric peptides were synthesized by adding the C‐terminal extension 28‐38 of the pituitary adenylate cyclase activating polypeptide (PACAP) to the sequences (1–27), (2–27), (3–27) and (6–27) of VIP. The capacity of these peptides to occupy the selective PACAP‐ and the non‐selective PACAP‐VIP receptors and to stimulate adenylate cyclase activity was studied in Chinese hamster ovary (CHO) cells expressing the recombinant receptors. The results were compared to those obtained with VIP and the corresponding VIP fragments.
The presence of the (28–38) PACAP extension increased at least 100‐fold the VIP‐ or VIP fragment affinities for the selective PACAP receptor but not for the non‐selective PACAP‐VIP receptors. Furthermore, on both receptors, the extension increased peptide intrinsic activity: VIP(3–28) was a partial agonist; while VIP(3–27)/PACAP(28–38) was as potent as VIP and was apparently a full agonist; VIP(6–28) had no intrinsic activity, but VIP(6–27)/PACAP(28–38) was a partial agonist.
These results suggest: (1) the presence of a specific domain for the (28–38) PACAP sequence on the selective PACAP receptor; and (2) a stabilizing effect of the (28–38) PACAP sequence on the structure of N‐terminally truncated VIP. © Munksgaard 1996.</description><subject>Adenylyl Cyclases - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cyclic AMP - biosynthesis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Iodine Radioisotopes</subject><subject>Membranes - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Neuropeptides - analysis</subject><subject>Neuropeptides - chemistry</subject><subject>Neuropeptides - metabolism</subject><subject>PACAP</subject><subject>PACAP receptors</subject><subject>peptide analogues</subject><subject>Pituitary Adenylate Cyclase-Activating Polypeptide</subject><subject>Radioligand Assay</subject><subject>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide</subject><subject>Receptors, Pituitary Hormone - metabolism</subject><subject>Receptors, Vasoactive Intestinal Peptide - metabolism</subject><subject>Recombinant Fusion Proteins - chemistry</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Sensitivity and Specificity</subject><subject>Vasoactive Intestinal Peptide - analysis</subject><subject>Vasoactive Intestinal Peptide - chemistry</subject><subject>Vasoactive Intestinal Peptide - metabolism</subject><subject>VIP</subject><subject>VIP receptors</subject><issn>0367-8377</issn><issn>1399-3011</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE9P2zAchq0JxArsI0yKdkDjkPBznfjPLlNJ-Tch1gMDiYuV2L9o7tKmxC60356EVt2u88WH930fWw8hXygktDtn04QypWIGlCZUKZ6EEkBmPFl9IINdtEcGwLiIJRPiIzn0fgrAUiaGB-RAKqqAw4A0I2tdcM08aqoo_Mbo61DGTJ5GC1wEZzHy-LzEucE-n4zy0SQKzXvx4WbyN5w11lUO_T-zGk1wLy6so2JuI6wqZwqzPib7VVF7_LS9j8ivy4v7_Dq-_Xl1k49uY5OKlMZlylPBaYlWpcAAsSyGhmbcMEExAzZEEGBBKqUEAhQi5VRarkrBFKdcsSNysuEu2qb7ow965rzBui7m2Cy9FjLLqATeFb9tiqZtvG-x0ovWzYp2rSno3rae6l6p7pXq3rbe2tarbvx5-8qynKHdTbd6u_z7Jn91Na7_g6zz8_GYKdoR4g3B-YCrHaFo_2gumMj0492VzuBe5T8mTxrYG2AxnD8</recordid><startdate>199610</startdate><enddate>199610</enddate><creator>GOURLET, PHILIPPE</creator><creator>VANDERMEERS, ANDRÉ</creator><creator>VANDERMEERS-PIRET, MARIE-CLAIRE</creator><creator>DE NEEF, PHILIPPE</creator><creator>ROBBERECHT, PATRICK</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>199610</creationdate><title>Addition of the (28-38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy</title><author>GOURLET, PHILIPPE ; VANDERMEERS, ANDRÉ ; VANDERMEERS-PIRET, MARIE-CLAIRE ; DE NEEF, PHILIPPE ; ROBBERECHT, PATRICK</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4741-b464761bed94030eeba2c156c371e5032e070d089997e00a74618d69b73961693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adenylyl Cyclases - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cyclic AMP - biosynthesis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Iodine Radioisotopes</topic><topic>Membranes - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Neuropeptides - analysis</topic><topic>Neuropeptides - chemistry</topic><topic>Neuropeptides - metabolism</topic><topic>PACAP</topic><topic>PACAP receptors</topic><topic>peptide analogues</topic><topic>Pituitary Adenylate Cyclase-Activating Polypeptide</topic><topic>Radioligand Assay</topic><topic>Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide</topic><topic>Receptors, Pituitary Hormone - metabolism</topic><topic>Receptors, Vasoactive Intestinal Peptide - metabolism</topic><topic>Recombinant Fusion Proteins - chemistry</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Sensitivity and Specificity</topic><topic>Vasoactive Intestinal Peptide - analysis</topic><topic>Vasoactive Intestinal Peptide - chemistry</topic><topic>Vasoactive Intestinal Peptide - metabolism</topic><topic>VIP</topic><topic>VIP receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GOURLET, PHILIPPE</creatorcontrib><creatorcontrib>VANDERMEERS, ANDRÉ</creatorcontrib><creatorcontrib>VANDERMEERS-PIRET, MARIE-CLAIRE</creatorcontrib><creatorcontrib>DE NEEF, PHILIPPE</creatorcontrib><creatorcontrib>ROBBERECHT, PATRICK</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International Journal of Peptide and Protein Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GOURLET, PHILIPPE</au><au>VANDERMEERS, ANDRÉ</au><au>VANDERMEERS-PIRET, MARIE-CLAIRE</au><au>DE NEEF, PHILIPPE</au><au>ROBBERECHT, PATRICK</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Addition of the (28-38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy</atitle><jtitle>International Journal of Peptide and Protein Research</jtitle><addtitle>Int J Pept Protein Res</addtitle><date>1996-10</date><risdate>1996</risdate><volume>48</volume><issue>4</issue><spage>391</spage><epage>396</epage><pages>391-396</pages><issn>0367-8377</issn><eissn>1399-3011</eissn><abstract>Chimeric peptides were synthesized by adding the C‐terminal extension 28‐38 of the pituitary adenylate cyclase activating polypeptide (PACAP) to the sequences (1–27), (2–27), (3–27) and (6–27) of VIP. The capacity of these peptides to occupy the selective PACAP‐ and the non‐selective PACAP‐VIP receptors and to stimulate adenylate cyclase activity was studied in Chinese hamster ovary (CHO) cells expressing the recombinant receptors. The results were compared to those obtained with VIP and the corresponding VIP fragments.
The presence of the (28–38) PACAP extension increased at least 100‐fold the VIP‐ or VIP fragment affinities for the selective PACAP receptor but not for the non‐selective PACAP‐VIP receptors. Furthermore, on both receptors, the extension increased peptide intrinsic activity: VIP(3–28) was a partial agonist; while VIP(3–27)/PACAP(28–38) was as potent as VIP and was apparently a full agonist; VIP(6–28) had no intrinsic activity, but VIP(6–27)/PACAP(28–38) was a partial agonist.
These results suggest: (1) the presence of a specific domain for the (28–38) PACAP sequence on the selective PACAP receptor; and (2) a stabilizing effect of the (28–38) PACAP sequence on the structure of N‐terminally truncated VIP. © Munksgaard 1996.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>8919060</pmid><doi>10.1111/j.1399-3011.1996.tb00856.x</doi><tpages>6</tpages></addata></record> |
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subjects | Adenylyl Cyclases - metabolism Amino Acid Sequence Animals Binding, Competitive CHO Cells Cricetinae Cyclic AMP - biosynthesis Dose-Response Relationship, Drug Iodine Radioisotopes Membranes - metabolism Molecular Sequence Data Neuropeptides - analysis Neuropeptides - chemistry Neuropeptides - metabolism PACAP PACAP receptors peptide analogues Pituitary Adenylate Cyclase-Activating Polypeptide Radioligand Assay Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide Receptors, Pituitary Hormone - metabolism Receptors, Vasoactive Intestinal Peptide - metabolism Recombinant Fusion Proteins - chemistry Recombinant Fusion Proteins - metabolism Sensitivity and Specificity Vasoactive Intestinal Peptide - analysis Vasoactive Intestinal Peptide - chemistry Vasoactive Intestinal Peptide - metabolism VIP VIP receptors |
title | Addition of the (28-38) peptide sequence of PACAP to the VIP sequence modifies peptide selectivity and efficacy |
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