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A chimeric VIP-PACAP analogue but not VIP pseudopeptides function as VIP receptor antagonists
V A Fishbein1, D H Coy, S J Hocart
1Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Peptides
|January 1, 1994
Summary
Researchers developed novel VIP receptor antagonists to study VIP's physiological roles. New pseudopeptides and chimeric analogues were synthesized and tested, showing potential for future research.
Area of Science:
- Biochemistry
- Molecular Pharmacology
- Peptide Chemistry
Background:
- Vasoactive intestinal peptide (VIP) plays crucial roles in various physiological processes.
- Assessing VIP's importance is hindered by a lack of specific and potent antagonists.
- Existing research necessitates the development of novel VIP receptor antagonists.
Purpose of the Study:
- To identify new VIP receptor antagonists.
- To explore the potential of pseudopeptides and chimeric analogues as VIP antagonists.
- To compare the efficacy of novel compounds with existing VIP antagonists.
Main Methods:
- Synthesis of pseudopeptides by inserting reduced peptide bonds into VIP (positions 2-8).
- Formation of a COOH-terminal chimeric analogue combining VIP(6-28) and PACAP(28-38).
- Assessment of antagonist activity by measuring inhibition of [125I]VIP binding to VIP receptors on guinea pig pancreatic acini.
Main Results:
- All synthesized peptides inhibited [125I]VIP binding to VIP receptors.
- Pseudopeptides demonstrated varying affinities, with [psi 3-4]VIP showing the highest affinity.
- The chimeric analogue VIP(6-28)-PACAP(28-38) exhibited significant antagonist potency.
- Interestingly, several pseudopeptides and a previously reported antagonist acted as agonists.
Conclusions:
- Novel pseudopeptide and chimeric analogues show promise as VIP receptor antagonists.
- The study highlights the complex agonist/antagonist activity of modified VIP analogues.
- Further research is needed to fully elucidate the therapeutic potential of these compounds.