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

FEBS Letters

Granoth, Ruth¹  Fridkin, Mati²  Gozes, Illana¹  Rubinraut, Sara² 

[1] Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel

关键词: Vasoactive intestinal peptide;    Keratinocyte cytotoxicity;    cGMP;    Lipophilic peptide;    Aurine-tricarboxylic acid;    VIP;    vasoactive intestinal peptide;    SNV;    stearyl-Nle17-VIP;    SNH;    stearyl-Nle17-neurotensin6–11VIP7–28;    St-KKYL-NH2;    stearyl-Lys-Lys-Tyr-Leu-NH2;    ATA;    aurine-tricarboxylic acid;    PACAP;    pituitary adenylate cyclase activating peptide;    VHA;    neurotensin6–11VIP7–28;    LDH;    lactate dehydrogenase;    GnRH;    gonadotropin releasing hormone;    CHI;    cycloheximide;    Pr;    propionyl;    K-SFM;    keratinocyte serum free medium;    EGF;    epidermal growth factor;    MEM;    minimal Eagle's essential medium;    FCS;    fetal calf serum;   

DOI  :  10.1016/S0014-5793(00)01629-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-neurotensin_6–11VIP_7–28, 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.

【 授权许可】

Unknown