Interferon induction: a conformational hypothesis.

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Abstract
The ability of polynucleotides or polynucleotide duplexes such as poly(I) .cntdot. poly(C) to induce interferon production may depend on the existence of certain stable glycosidic orientations. A slight increase in instability of 1-3 kcal/mol (1 cal = 4.184 J) in the conformational regions near 20.degree., 80.degree. and 160.degree. may lead to a loss of potency with respect to interferon induction. For a polynucleotide to exist in the overall conformation necessary for interferon induction, stability of glycosidic orientations near 20.degree., 80.degree. and 160.degree. 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 and 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. [These findings have relevance to the design of more potent interferon inducers and more selective antiviral polynucleotides.].