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Sequence‐dependence of the CD of synthetic double‐stranded RNAs containing inosinate instead of guanylate subunits

The CD spectra and melting profiles have been measured for nine synthetic double‐stranded RNAs containing I · C instead of G · C base pairs: poly[r(I) · r(C)], poly[r(I‐C) · r(I‐C)], poly[r(A‐I‐C) · r(I‐C‐U)], poly[r(A‐C) · r(I‐U)], poly[r(A‐I) · r(C‐U)], poly[r(A‐C‐C) · r(I‐I‐U)], poly[r(A‐A‐C) · r(I‐U‐U)], poly[r(A‐C‐U) · r(A‐I‐U)], and poly[r(A‐U‐C) · r(I‐A‐U)]. CD spectra have not previously been reported for the latter six of these polymers. The substitution of inosinate for guanylate led to recognizable CD differences, with all but two of the polymers having two resolved positive bands above 230 nm. Also, the I‐containing RNAs differed from their G‐containing counterparts in the almost complete absence of negative CD bands at long wavelengths and in the reduction of negative CD bands near 210 nm. First‐neighbor comparisons showed that the CD spectra of the I‐containing RNAs were consistent with the nearest‐neighbor sequences of the polymers, as previously shown for G‐containing RNAs (D. M. Gray, J.‐J. Liu, R. L. Ratliff, and F. S. Allen, Biopolymers (1981) 20, 1337–1382). Moreover, two of the first‐neighbor comparisons involved spectra of poly[r(A) · r(U)] and poly[r(I) · r(C)], polymers known to be in the A family of conformations in fibers (S. Arnott, D. W. L. Hukins, S. D. Dover, W. Fuller, and A. Hodgson, (1973) J. Mol. Biol. 81, 107–122). Thus, differences in the CD spectra of I‐ and G‐containing RNAs could be simply explained as resulting from differences in the hypoxanthine and guanine chromophores, without invoking differences in conformation. Finally, melting temperatures of the I‐containing RNAs were found to vary much less with base composition than do the melting temperatures of G‐containing RNAs, since A · U base pairs are closer to I · C than to G · C base pairs in stability.