Synthesis, DNA binding and anti-leukemic activity of an aminoacyl nucleolipid

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• 作者：Pradeepkumar Patel ; Emi Hanawa ; Reeta Yadav ; Uri Samuni ; Cecilia Marzabadi ; David Sabatino
• 关键词：Aminoacyl nucleolipid ; GRP78 DNA ; Bioconjugate ; Anti-leukemic activity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 September, 2013
• 年：2013
• 卷：23
• 期：18
• 页码：5086-5090
• 全文大小：1110 K

文摘

The synthesis and characterization of a new class of DNA binding molecule exhibiting potent and selective anti-leukemic activity is described. The synthesis of an aminoacyl nucleolipid was developed from an efficient EEDQ coupling strategy, in which a series of seven bioconjugates were synthesized in yields of 53-78 % . Guanosine bioconjugate 7, was used as building block for the synthesis of a target aminoacyl nucleolipid 14. Its GRP78 DNA binding affinity was confirmed by gel shift assay, CD spectroscopy, T_m measurements and dynamic light scattering experiments. Moreover, in a single dose (10 ¦ÌM) screen against a panel of 60 cancer cell lines, aminoacyl nucleolipid 14 was found to selectively trigger greater than 90 % cell death in a SR human leukemia cancer cell line. The reported aminoacyl nucleolipid represents a useful model for a new class of DNA binding molecules for the development of potent and selective anti-cancer agents.