Novel extended and branched N-terminal analogs of VIP

David Dangoor, Sara Rubinraut, Mati Fridkin, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The effects of vasoactive intestinal peptide (VIP) are primarily mediated through VPAC1 and VPAC2, receptors that are preferentially coupled to adenylate cyclase activation. As a large majority of the potent VIP antagonists have modifications in the N-terminal domain of the peptide, the effect of multiplication of this domain on VIP was examined with the aim of possibly amplifying peptide-receptor (VPAC1) activation. Several VIP analogs were designed and synthesized, each carrying multiplication of the N-terminal domain that was obtained by either linear tandem extension or by parallel branching. Circular dichorism (CD) analysis revealed that these extended/branched peptides maintained an α helical structure in organic environment, similar to VIP. A specific branched VIP analog was found to be slightly more potent towards VPAC1-related cAMP production as compared to VIP. This analog could have potential therapeutic value in several disorders, similar to VIP. Two branched N-terminal VIP sequences demonstrated superior receptor binding and activation as compared to two N-terminals in tandem. The results suggest that correct alignment of the VIP N-terminal region is important for receptor binding and activation. However, increased receptor binding was not directly associated with increased cAMP production suggesting steric dynamic interactions.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalRegulatory Peptides
Issue number1-2
StatePublished - 15 Nov 2006


  • CD
  • HT29 cells
  • Peptides
  • Receptor binding
  • VIP
  • VPAC1
  • cAMP


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