Abstract
Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.
Original language | English (US) |
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Pages (from-to) | 5536-5548 |
Number of pages | 13 |
Journal | Tetrahedron |
Volume | 62 |
Issue number | 23 |
DOIs | |
State | Published - Jun 5 2006 |
Keywords
- Bis-intercalator
- Dissociation kinetics
- Polyintercalation
- Rigid
- Spiro-cyclic linker
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry