Comparison of solid state and solution conformations of R and S epimers of 8,5'-cycloadenosine and their relevance to some enzymatic reactions.

Abstract

The C(5')-R epimer of 8,5'-cycloadenosine crystallizes in the monoclonic space group P2(1) (Z = 2) with unit cell dimensions a = 5.755 (1), b = 16.895 (1), and c = 5.511 (1) A and beta = 104.16 (1) degree. X-ray intensity data were measured on a diffractometer, and the crystal structure was determined by direct methods. Least-squares refinement converged at R = 0.037 for 1008 reflections. The conformation about the glycosyl bond is anti, as imposed by the 8,5' cyclization, with XCN = 29.8 degrees. The ribose ring adopts the unusual C(1')endo-O(4')exp (o1T) conformation with pseudo-rotation parameters P = 289.0 degrees and tau m = 490 degrees. The six-membered ring formed by the 8,5' linkage is approximately a half-chair with C(4') and O(4'), respectively, above and below a plane defined by the other four atoms. These results are compared with those previously reported for the corresponding S epimer [Haromy, T. P., Raleigh, J., & Sundaralingam, M. (1980) Biochemistry 19, 1718-1722]. The conformations of the sugar rings and the exocyclic groups of both epimers in the solid state are compared to the conformations in solution, as determined by analysis of the systems of proton-proton vicinal coupling constants from the 1H NMR spectra. The foregoing findings are employed to examine the role of the conformational parameters of adenosine and 5'-AMP in reactions catalyzed by the appropriate enzymes.