Interferon induction: a conformational hypothesis.

Abstract

The ability of polynucleotides or polynucleotide duplexes such as poly (I).poly(C) to induce interferon production is proposed to depend on the existence of certain stable glycosidic orientations. It appears that a slight increase in instability of 1-3 kcal/mole (1 cal = 4.184 J) in the conformational regions near 200, 800, and 1600 leads to a loss of potency with respect to interferon induction. Thus, it is proposed that, for a lynucleotide to exist in the overall conformation necessary for interferon induction, stability of glycosidic orientations near 200, 800, and 1600 may be necessary to confer flexibility and activity on polynucleotide structures. This proposed conformational triad of stable conformational regions essential to interferon induction is based on the results of conformational energy calculations of the glycosidic rotational profiles of adenosine, 7-deazaadenosine, inosine, and 7-deazainosine, as well as the conformational properties of other purine nucleoside analogs, and on inferences derived from calculations about the conformational effect in polynucleotides of removing the 2'-OH group.

Synthesis and biological activity of tubercidin analogs of ppp5'A2'p(5'A2'p)n5'A

“…enzymic transformation; for example, tubercidin 5'-triphosphate was not a substrate of adenosine deaminase (Ikehara & Fukui, 1974) or nucleoside phosphorylase (Bloch, 1975). Incorporation of tubercidin or its inosine counterpart, 7-deazainosine, into polynucleotides results in significant changes in interferon-inducing ability (DeClercq et al, 1974;Torrence et al, 1974) and nucleic acid conformation (Ikehara & Fukui, 1968;Bobst et al, 1976;Miles et al, 1979). Finally, Wreschner et al (1981b) and Floyd-Smith et al (1981) have noted that the preferred cleavage sites of RNase L all contain uridylate residues, which are complementary to the adenosines of 2-5A.…”

Porphyrin self-assembly as template for RNA?

“…7(a)) interestingly shows within vice versa adaptation between porphyrins and double stranded B-DNA helices a conformational shift from B-to (also RNA relevant) A-type, envisaged preferentially by the changes from 2'-endo to 3'-endo sugar pucker and from (high) anti to low-anti sugarbase linkages [27,37]. This special aptness especially for RNA patterns is further demonstrated by an optimization of helical interaction between single strand RNA and HpD (Fig.…”