Novel Side‐Chain Glucosylated and Adamantylated [Asp2/Glu2]Enkephalin Analogs: Synthesis and In Vitro Growth Inhibition of Human Tumor Cells |
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Authors: | Štefica Horvat Marijeta Kralj Milica Perc Ivanka Jerić Lidija Varga‐Defterdarović Andreja Jakas Maja Roščić Lidija Šuman Matija Gredičak |
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Affiliation: | 1. Division of Organic Chemistry and Biochemistry, Ru?er Bo?kovi? Institute, Zagreb 10002‐HR, Croatia;2. Division of Molecular Medicine, Ru?er Bo?kovi? Institute, Zagreb 10002‐HR, Croatia |
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Abstract: | A series of new backbone‐modified Leu‐ and Met‐enkephalin analogs ( 13 – 20 a and b ) were synthesized. Backbone manipulations involved the replacement of the Gly2 residue in Tyr‐Gly‐Gly‐Phe‐Leu/Met with side‐chain glucosylated or adamantylated D /L ‐aspartic or ‐glutamic acids. The in vitro antiproliferative activity of these compounds was evaluated for several cell lines and the results were compared with the effect of Met‐enkephalin, the native opioid growth factor. The tested compounds modestly inhibited the growth of the tumor cells (20–50% inhibition at millimolar concentrations). Among the tested compounds, Tyr‐D ‐Glu(AdNH)‐Gly‐Phe‐Met ( 20b ) showed significant antiproliferative activity, somewhat more pronounced on MCF‐7 (breast carcinoma) and MOLT‐4 (lymphoblastic leukemia) cells. |
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Keywords: | analogs in vitro antiproliferative activity Leu‐enkephalin Met‐enkephalin opioid peptides peptide synthesis |
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