VIP-derived sequences modified by N-terminal stearyl moiety induce cell death: The human keratinocyte as a model

Ruth Granoth, Mati Fridkin, Sara Rubinraut, Illana Gozes

Research output: Contribution to journalArticlepeer-review

Abstract

Vasoactive intestinal peptide (VIP) is a recognized growth factor affecting many cell types. We have previously developed a series of lipophilic VIP analogues containing an N-terminal covalently attached stearyl moiety. The current studies identified stearyl-Nle17-VIP and stearyl-Nle17-neurotensin6-11VIP7-28, acting at μM concentrations, as cytotoxic to human keratinocytes. The core C-terminal active VIP-derived peptide, stearyl-Lys-Lys-Tyr-Leu-NH2 (St-KKYL-NH2), was identified as being responsible for the observed cytotoxicity. Cytotoxicity coincided with marked reduction in intracellular cyclic GMP and was abolished by co-treatment with the endonuclease inhibitor, aurine-tricarboxylic acid, suggesting apoptotic mechanisms. Stearyl-VIP derivatives thus offer lead compounds for future drug development against hyperproliferative skin conditions. Copyright (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalFEBS Letters
Volume475
Issue number2
DOIs
StatePublished - 16 Jun 2000

Keywords

  • Aurine-tricarboxylic acid
  • Keratinocyte cytotoxicity
  • Lipophilic peptide
  • Vasoactive intestinal peptide
  • cGMP

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