tailieunhanh - Báo cáo khoa học: Interaction of G-rich GT oligonucleotides with nuclearassociated eEF1A is correlated with their antiproliferative effect in haematopoietic human cancer cell lines

G-rich GT oligonucleotides with a different content of G clusters have been evaluated for their ability to exert cytotoxicity and to bind to nuclear-associated proteins in T-lymphoblast CCRF-CEM cells. Only the oligomers that did not form G-based structures or had a poor structure, under physiological conditions, were able to exert significant cellular growth inhibition effect. | iFEBS Journal Interaction of G-rich GT oligonucleotides with nuclear-associated eEFIA is correlated with their antiproliferative effect in haematopoietic human cancer cell lines Bruna Scaggiante1 Barbara Dapas1 Gabriele Grassi2 and Giorgio Manzini1 1 Department of Biochemistry Biophysics and Macromolecular Chemistry University of Trieste Italy 2 Department of Clinical Morphological and TechnologicalSciences Division of InternalMedicine University of Trieste Italy Keywords aptamers CCRF-CEM cell growth inhibition eEF1A G-rich GT oligonucleotides Correspondence B. Scaggiante Molecular Biology Section Department of Biochemistry Biophysics and Macromolecular Chemistry via Giorgeri 1 34127-Trieste Italy Fax 39 040558 3691 Tel. 39 040558 3678 E-mail scaggiante@ Received 30 August 2005 revised 12 January 2006 accepted 18 January 2006 doi G-rich GT oligonucleotides with a different content of G clusters have been evaluated for their ability to exert cytotoxicity and to bind to nuclear-associated proteins in T-lymphoblast CCRF-CEM cells. Only the oligomers that did not form G-based structures or had a poor structure under physiological conditions were able to exert significant cellular growth inhibition effect. The cytotoxicity of these oligomers was related to their binding to the nuclear-associated eEF1A protein but not to the recognition of nucleolin or other proteins. In particular GT oligomers adopting a conformation compatible with G-quadruplex did not exert cytotoxicity and did not bind to eEF1A. The overall results suggest that the ability of oligomers to adopt a G-quadruplex-type secondary structure in a physiological buffer containing 150 mM NaCl is not a prerequisite for antiproliferative effect in haematopoietic cancer cells. The cytotoxicity of G-rich GT oligomers was shown to be tightly related to their binding affinity for eEF1A protein. Single-stranded DNA may act as aptamer in recognizing proteins with an .