Solution structure and stability of a disulfide cross-linked nucleopeptide duplex

NMR methods are used to study the structure and stability of the duplex formed by the nucleopeptide [Ac-Cys-Gly-Ala-Hse(p^3ʹdGCATGC)-Ala-OH]2[S-S], in which the oligonucleotide is self-complementary and the cysteine residues of the two peptide chains form a Adisulfide bridge; thermal transitions and NMR-derived structural calculations are Aconsistent with a 3-D structure in which the oligonucleotide forms a standard B-DNA Ahelix without significant distortions; the peptide chains are relatively disordered in solution and lie Ain the minor groove of the DNA helix; this nucleopeptide duplex exhibits a high melting Atemperature, indicating that peptide–oligonucleotide conjugates containing cysteines are Asuitable molecules to establish cross-links between DNA strands and stabilize the duplex.