Conformational study of trinucleoside tetraphosphate d(pCpGpCp): Transition of right‐handed form to left‐handed form

Using the semiempirical potential functions, conformational energies of the model compounds DMP − , d(pCp), d(pGp), and d(pCpGpCp) are calculated, and the B → Z transition is discussed along the pseudorotational path of the sugar ring. For dimethylmonophosphate anion, DMP − , the energy contour map is presented and the stabilities of the phosphodiester conformations discussed. For the sugar ring without the base attached, the minimum energies for each sugar‐puckering form are calculated along the pseudorotational path. The energy barrier of the interconversion between the C(3′)‐ endo form and the C(2′)‐ endo form is calculated to be about 2.0 kcal/mol. From the conformational energy calculations of the interconversions of mononucleoside diphosphates, d(pCp) and d(pGp), between the C(2′)‐ endo conformer and the C(3′)‐ endo conformer, the purine sugar segment is known to be more convertible than the pyrimidine sugar segment. The results also support the finding that the pseudorotational transition occurred with the O(1′)‐ endo form more easily than with the O(1′)‐ exo form. Based on the results of conformational studies of DMP − , d(pCp), and d(pGp), a topological transition of the handedness of the model compound, d(pCpGpCp), is studied. The left‐handed Z‐form is found to be less stable by about 8.5 kcal/mol than is the right‐handed B‐form. The energy barrier of the Z → B transition is calculated to be about 17.4 kcal/mol. The contributions of the electrostatic and nonbonded energies to the energy barrier are discussed in connection with the conformation changes of the model compound, d(pCpGpCp).