Synthesis and bioactivity of a Goralatide analog with antileukemic activity

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 15; pp. 5056 - 5060
• Main Authors: Li, Zhiliang, Lebedyeva, Iryna O., Golubovskaya, Vita M., Cance, William G., Alamry, Khalid A., Faidallah, Hassan M., Dennis Hall, C., Katritzky, Alan R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2015
• Subjects: Anticancer; Antileukemic; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Goralatide; HEK293 Cells; HL-60 Cells; Human Umbilical Vein Endothelial Cells; Humans; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - toxicity; Peptide; Peptidomimetic; Antileukemic; Anticancer; Peptidomimetic; Peptide; Goralatide
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2015.04.061

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Natural tetrapeptide Goralatide (AcSDKP) is a selective inhibitor of primitive haematopoietic cell proliferation. It is not stable in vivo and decomposes within 4.5min when applied to live cells. In this work we developed an analog of Goralatide that exhibits cytotoxicity towards human myeloid HL-60, HEL, Nalm-6 leukemia cells, endothelial HUVEC, glioblastoma U251 and transformed kidney 293T cells. The Goralatide analog showed significant stability in organic solution with no tendency to degrade oxidatively.