ABSTRACT
The poly(dA-dU) and poly(dI-dC) duplexes have very similar thermostabilities (Tm). This similarity extends also to the pyrimidine 5-methyl group-containing poly(dA-dT) and poly(dI-m5dC). The differences between chemical structures of the A:U and I:C or the A:T and I:m5C base-pairs seem to be unimportant for the thermostability of the DNA. However, on the insertion of an amino group into position 2 of the purines the similarities disappear. Thermostabilities of poly(n2dA-dU) and poly(dG-dC) as well as the poly(n2dA-dT) and poly(dG-m5dC) are radically different. This is also the case with their other 5-substituted pyrimidine-containing derivatives, the 5-ethyl, 5-n-butyl and 5-bromo analogues. The G:C-based polynucleotides are more stable by an average of 40 degrees C than the n2A.U-based ones. Poly(dA,n2dA-dT)-s containing various proportions of A and n2A as well as the natural DNA of S-2L cyanophage that contains n2A bases instead of A were also studied. It was found that dependence of Tm on the n2A-content was non-linear and that the lower Tm is not the consequence of a particular nucleotide sequence. The possible structural reasons for the lower thermostabilization of these B-DNAs by the n2A:T base-pair as compared to the G:C are discussed.
Subject(s)
2-Aminopurine/analogs & derivatives , DNA/chemistry , 2-Aminopurine/chemistry , Absorption , Bacteriophages/chemistry , Base Composition , Circular Dichroism , Deoxyribonucleotides/chemistry , Molecular Structure , Nucleic Acid Conformation , Nucleic Acid Heteroduplexes , Purines/chemistry , Pyrimidines/chemistry , Structure-Activity Relationship , Ultraviolet RaysABSTRACT
Poly(amino2dA-dT) easily isomerizes into a non-B conformer which most authors think is an A-form. We synthesized new DNA analogs poly(amino2dA-ethyl5dU) and poly(amino2dA-dU) to show that they do not prefer this conformer. Hence the putative A-form is, like Z-DNA of poly(dG-dC) but unlike A-DNA, strongly stabilized by the methyl group in position 5 of the pyrimidine base. In addition, the putative A-form is induced by divalent cations while it does not need any alcohol to be stable, both properties being typical for Z-DNA again but quite unusual with A-DNA. Despite these similarities, the putative A-form is also distinct from Z-DNA, as poly(amino2dA-dT) is shown to isomerize into a Z-form in the NaCl + NiCl2 solvent system like poly(dA-dT). The present data indicate that the putative A-form of poly(amino2dA-dT) differs in a significant way from all canonical conformers of DNA. Furthermore, the studies of the poly(amino2dA-dT) family of polydeoxynucleotides reveal a novel type of conformational switch in DNA. We also report the B-Z transitions of poly(amino2dA-ethyl5dU) and poly(amino2dA-dU) and their transitions into the putative A-form in aqueous alcohol solutions.
