PKA OF CYTOSINE ON THE 3RD STRAND OF TRIPLEX DNA - PRELIMINARY POISSON-BOLTZMANN CALCULATIONS

The energetics of formation of a triple-helical structure in homopurin e-homopyrimidine mixtures has been modeled using Poisson-Boltzmann cal culations. Oligomers with the sequence d(TC)(n) and d(AG)(n) form hydr ogen-bonded triple-helical structures of the form B(TC)(n) . d(AG)(n) . d(TC+)(n). The third base, a pyrimidine in this case, forms Hoogstee n-type hydrogen bonds with the purine, requiring that the cytosine res idues of the third strand protonate at N3. The pK(a) of cytosine, 4.3 in the isolated solvated molecule, is raised by the strong electrostat ic field in the triple helix. We have done calculations of the effecti ve pK(a) of this cytosine and compared the results with experimental s tudies of triple-helix formation as a function of pH. This provides a test of various models of the dielectric constant for tripler DNA and its local environment. (C) 1998 John Wiley & Sons, Inc.