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Convenient synthesis of NCS-chromophore metabolite isosteres: binding agents for bulged DNA microenvironments
Authors:Lin Yiqing  Jones Graham B  Hwang Geum-Sook  Kappen Lizzy  Goldberg Irving H
Institution:Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA.
Abstract:A designed molecule with capacity to bind DNA bulges (20) has been prepared from readily available starting materials. The spirocyclic template was modeled on a metabolite of neocarzinostatin chromophore (NCSi-gb) and is equipped with functionality to enable convenient bioassay. Preliminary studies confirm binding at specific bulged sequences and induction of polymerase-mediated slippage events. The target compound offers a convenient means to study affinity for unique bulged motifs and for use as a molecular biology reagent.
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