PKa of cytosine on the third strand of triplex DNA: Preliminary Poisson-Boltzmann calculations

• Published in: International journal of quantum chemistry Vol. 70; no. 6; pp. 1177 - 1184
• Main Authors: Pack, George R., Wong, Linda, Lamm, Gene
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 1998
• Subjects: acid dissociation constant; dielectric constant; pKa shift; triple helix
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/(SICI)1097-461X(1998)70:6<1177::AID-QUA7>3.0.CO;2-X

The energetics of formation of a triple‐helical structure in homopurine–homopyrimidine mixtures has been modeled using Poisson–Boltzmann calculations. Oligomers with the sequence d(TC)n and d(AG)n form hydrogen‐bonded triple‐helical structures of the form d(TC)n⋅d(AG)n⋅d(TC+)n. The third base, a pyrimidine in this case, forms Hoogsteen‐type hydrogen bonds with the purine, requiring that the cytosine residues of the third strand protonate at N3. The pKa of cytosine, 4.3 in the isolated solvated molecule, is raised by the strong electrostatic field in the triple helix. We have done calculations of the effective pKa of this cytosine and compared the results with experimental studies of triple‐helix formation as a function of pH. This provides a test of various models of the dielectric constant for triplex DNA and its local environment. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 1177–1184, 1998