Structural analysis of covalent peptide dimers, bis(pyridine-2-carboxamidonetropsin)(CH[sub 2])[sub 3][sup 6], in complex with 5[prime]-TGACT-3[prime] sites by two-dimensional NMR

The peptide pyridine-2-carboxamidonetropsin (2-PyN) binds specifically in the minor groove of 5[prime]-(A,T)G-(A,T)C(A,T)-3[prime] 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[sub 2])[sub 3[minus]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[prime]-TGACT-3[prime] site reveal that the dimeric peptides bind as intramolecular dimers with nearly identical geometry and peptide-DNA contacts as in the (2-PyN)[sub 2][center dot]5[prime]-TGACT-3[prime] complex. 13 refs., 9 figs., 2 tabs.