Interferon Induction: A Conformational Hypothesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 76; no. 3; pp. 1018 - 1021
• Main Authors: Miles, Douglas L., Miles, Daniel W., Eyring, Henry
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.03.1979; National Acad Sciences
• Subjects: Adenosine; Calorimetry; Coordinate systems; DNA; Glycosides; Inosine; Interferon Inducers; Interferons; Nucleic Acid Conformation; Nucleic acids; Nucleosides; Nucleotides; Poly I-C; Polynucleotides; Purine nucleosides; Purines; Rotation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.76.3.1018

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 20 degrees, 80 degrees, and 160 degrees leads to a loss of potency with respect to interferon induction. Thus, it is proposed that, for a polynucleotide to exist in the overall conformation necessary for interferon induction, stability of glycosidic orientations near 20 degrees, 80 degrees, and 160 degrees 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.