Communication between noncontacting macromolecules

Abstract

We present a quantitative experimental demonstration of solventmediated communication between noncontacting biopolymers. We show that changes in the activity of a solvent component brought about by a conformational change in one biopolymer can result in changes in the physical properties of a second noncontacting biopolymer present in solution. Specifically, we show that the release of protons on denaturation of a donor polymer (in this case, a four-stranded DNA tetraplex, iDNA) modulates the melting temperature of a noncontacting, acceptor polymer [in this case poly(A)]. In addition to such proton-mediated cross talk, we also demonstrate counterion-mediated cross talk between noncontacting biopolymers. Specifically, we show that counterion association͞release on denaturation of native salmon sperm DNA (the donor polymer) can modulate the melting temperature of poly(dA)⅐poly(dT) (the acceptor polymer). Taken together, these two examples demonstrate how poly(A) and poly(dA)⅐poly(dT) can serve as molecular probes that report the pH and free salt concentrations in solution, respectively. Further, we demonstrate how such through-solvent dialogue between biopolymers that do not directly interact can be used to evaluate (in a model-free manner) association͞dissociation reactions of solvent components (e.g., protons, sodium cations) with one of the two biopolymers. We propose that such through-solution dialogue is a general property of all biopolymers. As a result, such solvent-mediated cross talk should be considered when assessing reactions of multicomponent systems such as those that exist in essentially all biological processes.

Conformational energetics of stable and metastable states formed by DNA triplet repeat oligonucleotides: Implications for triplet expansion diseases

“…Oligonucletides were synthesized and purified as previously described (35,36). Concentrations were determined optically in 10 mM Na cacodylate, pH 7.0, buffer by using a Varian 300 UV͞Vis spectrophotometer.…”

“…Temperature-dependent UV absorption measurements were conducted and analyzed as previously described by using an Aviv (Lakewood, NJ) DS14 UV͞VIS spectrophotometer equipped with a five-cell thermoelectric cell holder (35,(39)(40)(41). Unless otherwise indicated, oligonucleotide concentrations were always 1 M in single strand or duplex.…”

DNA nanomachines and nanostructures involving quadruplexes

“…Proton release/uptake may be so high that the i-motif structure may be used as a proton donor/acceptor. 29 The telomeric repeat (CCCTAA) 4 can form the i-motif; its halfdissociation temperature (T m ) is 39 • C at pH 6 but is only 20 • C at neutral pH. 30…”

The energetics of i‐DNA tetraplex structures formed intermolecularly by d(TC5) and intramolecularly by d[(C5T3)3C5]

“…We previously have suggested that biological processes may lead to localized changes in pH that can stabilize pH-dependent DNA structures such as the i-DNA. 56 The energetic and environment-dependent differences for i-DNA/G-quartet structures relative to duplex DNA may allow for selective control of these structures, which might potentially form transiently during critical regulatory events. The thermodynamic estimates given here suggest that the cost of replacing a conventional Watson-Crick duplex domain with a combination of i-DNA and G-quadruplex structures is energetically reasonable.…”

“…We previously used DSC to detect and characterize coupled conformational transitions in i-DNA and poly rA, a coupling that resulted in communication between noncontacting nucleic acid species. 56,57 In this study, we focus on characterizing the energetics of tetraplex formation for the prototype d(TC 5 ) oligomer, which was the first oligonucleotide shown to adopt the i-DNA structure. We also characterize the related oligomer d[(C 5 T 3 ) 3 C 5 ] in which the four d(TC 5 ) strands are linked together by three all-thymine loops to form an intramolecular rather than intermolecular tetraplex.…”