Structural Analysis of Covalent Peptide Dimers, Bis(pyridine-2-carboxamidonetropsin)(CH2)3–6, in Complex with 5′-TGACT-S′ 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) (CH2)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. © 1993, American Chemical Society. All rights reserved.