Nucleic acid bioconjugates have been successfully applied in anti-cancer research programs aimed at fighting the cancer epidemic en route towards the development of effective and safe treatment methods. Their widespread use stems from the ability to accelerate the drug development process by conjugating chemical functionality that may improve the pharmacology of the nucleoside. This therapeutic strategy has been realized with small molecule nucleosides and those derived from lengthy oligonucleotides. Considering the utility of nucleic acid bioconjugates in anti-cancer applications, our research aims to explore the synthesis, characterization and therapeutic potential of novel nucleic acid bioconjugates. These are based on (a) aminoacyl nucleolipids, from which a simple and efficient synthesis strategy has been developed for this new class of DNA binding molecule. This nucleic acid based bioconjugate displayed GRP78 oncogene binding affinity (KD: 0.25 mM) and selective anti-leukemic activity in a single dose (10 �M) screen against a panel of 60 cancer cell lines.1 (b) The synthesis, bio-physical properties and oncogene photocleavage acitivty of a phthalocyanine-linked oligonucleotide for potential photodynamic therapy applications. This novel conjugate was synthesized and characterized using HPLC, mass spectrometry, UV-Vis spectroscopy and thermal denaturation. The ability of this conjugate to damage GRP78 DNA/mRNA was validated.2 This presentation will highlight our most recent contributions to the flourishing field of bioorthogonal chemistry applied to the synthesis of nucleic acid bioconjugates for anti-cancer applications. References. (1)  Patel, P.; Hanawa, M.; Yadav, R.; Samuni, U.; Marzabadi, C.; Sabatino, D. Synthesis, DNA binding andanti-leukemic activity of an aminoacyl nucleolipid. Bioorg. Med. Chem. Lett, 2013 , 23, 5086-5090.  (2)Patel, P.; Patel, H.; Borland, E.; Gorun, S.M.; Sabatino, D. Chemically RobustFluorophthalocyanine-Oligonucleotide Bioconjugates and their GRP78 Oncogene Photocleavage Activity.ChemComm. 2014 ,Accepted Manuscript. (DOI:  10.1039/C4CC00703D)

Nucleic acid bioconjugates in anticancer applications

248th National Meeting (2014)

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