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
Hauptverfasser: GOURLET, PHILIPPE, VANDERMEERS, ANDRÉ, VANDERMEERS-PIRET, MARIE-CLAIRE, DE NEEF, PHILIPPE, ROBBERECHT, PATRICK
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container_issue 4
container_start_page 391
container_title International Journal of Peptide and Protein Research
container_volume 48
creator GOURLET, PHILIPPE
VANDERMEERS, ANDRÉ
VANDERMEERS-PIRET, MARIE-CLAIRE
DE NEEF, PHILIPPE
ROBBERECHT, PATRICK
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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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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ispartof International Journal of Peptide and Protein Research, 1996-10, Vol.48 (4), p.391-396
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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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