Stereochemistry of 2′-5′ Linked Nucleic Acids: Crystal and Molecular Structure of Ammonium Adenylyl-2′, 5′-Adenosine Tetrahydrate: A Core Fragment of 2′-5′ Oligo A′s Produced by Interferon Induced Adenylate Synthetased

Abstract

The preponderance of 3′-5′ phosphodiester links in nucleic acids is well known. Albeit less prevalent, the 2′-5′ links are specifically utilised in the formation of ‘lariat’ in group II introns and in the msDNA-RNA junction in myxobacterium. As a sequel to our earlier study on cytidylyl-2′,5′-adenosine we have now obtained the crystal structure of adenylyl-2′,5′-adenosine (A2′p5′A) at atomic resolution. This dinucleoside monophosphate crystallises in the orthorhombic space group P2₁2₁2₁ with a= 7.956(3)Å, b = 12.212(3)Å and c = 36.654 (3) Å. CuKα intensity data were collected on a diffractometer. The structure was sloved by direct methods and refined by full matrix least squares methods to R = 10.8 %. The 2′ terminal adenine is in the commonly observed anti (χ₂ =−161°) conformation and the 5′ terminal base has a syn (χ₁ = 55°) conformation more often seen in purine nucleotides. A noteworthy feature of A2′p5′ A is the intranucleotide hydrogen bond between N3 and 05′ atoms of the 5′ adenine base. The two furanose rings in A2′ p5′ A show different conformations-C2′ endo, C3′ endo puckering for the 5′ and 2′ ends respectively. In this structure too there is a stacking of the purine base on the ribose 04′ just as in other 2′-5′ dinucleoside structures, a feature characteristically seen in the left handed ZDNA. In having syn, anti conformation about the glycosyl bonds, C2′ endo, C3′ endo mixed sugar puckering and N3–05′ intramolecular hydrogen bond A2′p5′ A resembles its 3′-5′ analogue and several other 2′-5′ dinucleoside monophosphate structures solved so far. Striking similarities between the 2′-5′ dinucleoside monophosphate structures suggest that the conformation of the 5′-end nucleoside dictates the conformation of the 2′ end nucleoside. Also, the 2′-5′ dimers do not favour formation of miniature classical double helical structures like the 3′-5′ dimers. It is conceivable, 2–5(A) could be using the stereochemical features of A2′p5′ A which accounts for its higher activity.