Structural analysis of covalent peptide dimers, bis(pyridine-2-carboxamidonetropsin)(CH_2)_(3-6), in complex with 5'-TGACT-3' sites by two-dimensional NMR

Abstract

The peptide pyridine-2-carboxamidonetropsin (2-PyN) binds specifically in the minor groove of 5'-(A,T)G(A,T)C(A,T)-3' sequences as a side-by-side antiparallel dimer. Tethering two 2-PyN ligands through the nitrogens of the central pyrrole rings with propyl, butyl, pentyl and hexyl linkers affords covalent peptide dimers, bis(pyridine-2-carboxamide-netropsin)(CH_2)_(3-6), which bind in the minor groove of DNA with increased binding affinities and improved sequence specificities. Two-dimensional NMR studies of the complexes formed upon binding of these covalent peptide dimers to an oligonucleotide containing a 5'-TGACT-3' site reveal that the dimeric peptides bind as intramolecular dimers with nearly identical geometry and peptide-DNA contacts as in the (2-PyN)_2•5'-TGACT-3' complex.

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