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Thermodynamic effect of 6‐thioguanine substitution in duplex DNA
Author(s) -
Dunham Stephen Uldrich
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a293-a
Subject(s) - isothermal titration calorimetry , differential scanning calorimetry , duplex (building) , chemistry , myeloid leukemia , titration , acute lymphocytic leukemia , calorimetry , cytotoxicity , leukemia , dna , cancer research , biochemistry , medicine , lymphoblastic leukemia , thermodynamics , in vitro , physics
6‐Thioguanine (6SG) has been used for the past thirty years as an anti‐cancer agent in maintenance chemotherapy for childhood acute lymphoblastic leukemia as well as acute myeloid leukemia. Despite its long‐standing clinical use, a molecular basis of the cytotoxicity associated with 6SG remains an active area of research. To further understand the structural changes associated with DNA duplexes containing 6SG, we have studied and compared the thermodynamic properties of an 11‐base pair duplex in which the central G residue is replaced by 6SG. A combination of temperature dependent UV‐Visible spectroscopy, differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC) were used to characterize the thermodynamic effects of 6SG incorporation. Support: Moravian College, Colby College, NSF CHE‐0216655