Superactive lipophilic peptides discriminate multiple vasoactive intestinal peptide receptors

I. Gozes*, G. Lilling, R. Glazer, A. Ticher, I. E. Ashkenazi, A. Davidson, S. Rubinraut, M. Fridkin, D. E. Brenneman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

To distinguish vasoactive intestinal peptide (VIP) receptors in the brain- mediating neurotransmission and neurotrophism, potent VIP analogues were designed. Using a single amino acid substitution and the addition of a fatty acyl moiety, an analogue was devised that exhibited both a 100-fold greater potency than VIP and specificity for a VP receptor associated with neuronal survival. This VIP agonist increased neuronal survival via a cAMP-independent mechanism. Identical chemical modification of a prototype VIP antagonist (Met-Hybrid, Neurotensin6-11-VIP7-26) also resulted in a 100-fold greater potency in blocking VIP-mediated increases in neuronal survival. Blockade of circadian activity rhythms was limited to VIP antagonists that could inhibit VIP-mediated increases in cAMP. These lipophilic peptides provide novel tools in receptor discrimination and drug design.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume273
Issue number1
StatePublished - 1995

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