Thermodynamic linkage analysis of pH-induced folding and unfolding transitions of i-motifs.
We describe the pH-induced folding/unfolding transitions of i-motifs by a linkage thermodynamics-based formalism in terms of three pKa's of cytosines, namely, an apparent pKa in the unfolded conformation, pKau, and two apparent pKa's in the folded state, pKaf1 and pKaf2. For the 5'-TTACCCACCCTACCCACCCTCA-3' sequence from the human c-MYC oncogene promoter region, the values of pKau, pKaf1, and pKaf2 are 4.8, 6.0, and 3.6, respectively. With these pKa's, we calculate the differential number of protons bound to the folded and unfolded states as a function of pH. Analysis along these lines offers an alternative interpretation to the experimentally observed shift in the pH-induced unfolded-to-i-motif transitions to neutral pH in the presence of cosolvents and crowders.
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.
Byul G
BG
Kim
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada. Electronic address: chalikan@phm.utoronto.ca.
Tigran V
TV
Chalikian
D020029:Base Pairing; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D016259:Genes, myc; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D013816:Thermodynamics
D003596:Cytosine; D004247:DNA
Conformational transitions; Cytosines; DNA; Linkage thermodynamics; i-motif