Triplex formation by oligodeoxyribonucleotides involving the formation of X.U.A triads

• Published in: Biochemistry (Easton) 1993-03, Vol.32 (12), p.2999-3004
• Main Authors: MILLER, P. S, CUSHMAN, C. D
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Base Composition; Base Sequence; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Dna, deoxyribonucleoproteins; Fundamental and applied biological sciences. Psychology; Hot Temperature; Hydrogen Bonding; Hydrogen-Ion Concentration; Molecular Sequence Data; Molecular Structure; Nucleic acids; Oligodeoxyribonucleotides - chemistry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00063a010

The stabilities of oligodeoxyribonucleotide triplexes containing a single pyrimidine-purine base pair, which interrupts an otherwise purine-pyrimidine base pair motif, were studied by UV melting experiments. The oligomer systems consisted of an oligodeoxyribonucleotide target duplex d-GAAGAAAAAAYAAAA/d-TTTTZTTTTTTCTTC, I.II(Y.Z), or d-GAAGAAAAAGUGAAA/d-TTTCACTTTTTCTTC, IV.V(U.A), where Y.Z is C.G, T.A, or U.A and U is deoxyuridine. The third strand oligodeoxyribopyrimidine was d-CTTCTTTTTTXTTTT, III(X), or d-CTTCTTTTTCXCTTT, VI(X), where C is 5-methyldeoxycytidine. Triplexes were observed in the system III.I.II(X.C.G) when X was T or U. This may involve formation of T. or U.C.G triads in which the 4-carbonyl of T or U serves as a hydrogen bond acceptor for the N4-amino group of C. Triplex formation between III(X) and I.II(T.A) was only observed when X was G. In contrast to T.A or C.G, it appears a U.A base pair in the duplex target is a much more versatile participant in triad formation. Thus, stable triplexes were observed in III.I.II(X.U.A) and in VI.IV.V(X.U.A) when X was C, C, T, or U. The formation of a T.U.A or U.U.A triad can occur if the T or U of III translates approximately 1.4 A into the major groove, thereby allowing the 3-NH of T or U to donate a hydrogen bond to the 4-carbonyl oxygen of U in the duplex. Formation of C. or C.U.A base triads could involve formation of a single hydrogen bond between the third strand N4-amino group of C or C and the 4-carbonyl group of U of the target.