Threading polyintercalators

ORGN 258

Brent L. Iverson1, Jeeyeon Lee, jyl@mail.utexas.edu2, Vladimir Guelev3, and Yongjun Chu, yjchu@mail.cm.utexas.edu1. (1) Department of Chemistry and Biochemistry, The University of Texas at Austin, 1 University Station, A5300, Austin, TX 78712, (2) Department of Chemistry and Biochemistry, University of Texas at Austin, 24th street and Speedway, Austin, TX 78712, (3) Department of Chemistry & Biochemistry, The University of Texas at Austin, 1 University Station, Austin, TX 78712
My laboratory has been exploring the use of aromatic donor-acceptor interactions to control folding and assembly in aqueous solution. As part of this effort, the relatively electron deficient 1,4,5,8-naphthalene diimide (NDI) has been investigated as a DNA intercalator. Previous work revealed that NDI is a threading intercalator. The threading topology has been exploited in the design of threading polyintercalators in which several NDI units are linked in a head-to-tail arrangement by flexible peptide chains. Combinatorial studies identified two NDI dimers with distinct sequence preferences when bound to double stranded DNA, and NMR structural analysis revealed that one dimer placed the linker in the DNA minor groove, while the other placed the linker in the major groove. Combining these into a hybrid molecule has produced a threading tetraintercalator and NMR structural analysis has verified binding with the linkers alternating between the DNA grooves as predicted, analogous to the way a snake might climb a ladder.
 

Frontiers in Bio-organic Chemistry and Chemical Biology
8:00 AM-11:55 AM, Monday, 14 March 2005 Convention Center -- Ballroom 20 C-D, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005