Tuning the selectivity of triplex DNA receptors

Huang, Haidong; Tlatelpa, Peter C.

doi:10.1039/c4cc07805e

Cited by 10 publications

(11 citation statements)

References 28 publications

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“…7). 49 The abasic site-bridged triplex has a more rigid, cyclic linker structure, and can be expected to be slightly better preorganized towards ligand binding than the C3-containing analogue with its acyclic backbone. However the abasic sitecontaining triplex will almost certainly suffer the steric clash that prevents binding mode A, resulting in an entropically less favorable situation.…”

Section: Discussionmentioning

confidence: 99%

Effect of preorganization on the affinity of synthetic DNA binding motifs for nucleotide ligands

Vollmer

Richert

2015

Org. Biomol. Chem.

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Triplexes with a gap in the purine strand have been shown to bind adenosine or guanosine derivatives through a combination of Watson-Crick and Hoogsteen base pairing. Rigidifying the binding site should be advantageous for affinity. Here we report that clamps delimiting the binding site have a modest effect on affinity, while bridging the gap of the purine strand can strongly increase affinity for ATP, cAMP, and FAD. The lowest dissociation constants were measured for two-strand triple helical motifs with a propylene bridge or an abasic nucleoside analog, with Kd values as low as 30 nM for cAMP in the latter case. Taken together, our data suggest that improving preorganization through covalent bridges increases the affinity for nucleotide ligands. But, a bulky bridge may also block one of two alternative binding modes for the adenine base. The results may help to design new receptors, switches, or storage motifs for purine-containing ligands.

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Section: Discussionmentioning

confidence: 99%

Effect of preorganization on the affinity of synthetic DNA binding motifs for nucleotide ligands

Vollmer

Richert

2015

Org. Biomol. Chem.

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“…However, when as econd base pairing interaction is allowed to takep lace, by leaving ag ap as binding site in the center of at riple helix, dissociation constants for complexesw ithn ucleotidesr each the nanomolar range. [14][15][16][17][18][19] With such ac ombination of Watson-Crick and Hoogsteen base pairing (Figure 1b), nucleoside phosphates can be bound with affinitiesh igher than those found for non-DNA binding motifs, such as pyridinium tripods, [20] artificial tweezers, [21] scorpiandr eceptors, [22] or copperc omplexes. [23] Further,g ood binding selectivities can be achieved, [15] and intracellularl evels of purine nucleotides can be affected.…”

Section: Introductionmentioning

confidence: 98%

DNA Triplexes That Bind Several Cofactor Molecules

Vollmer

Richert

2015

Chemistry A European J

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Cofactors are critical for energy-consuming processes in the cell. Harnessing such processes for practical applications requires control over the concentration of cofactors. We have recently shown that DNA triplex motifs with a designed binding site can be used to capture and release nucleotides with low micromolar dissociation constants. In order to increase the storage capacity of such triplex motifs, we have explored the limits of ligand binding through designed cavities in the oligopurine tract. Oligonucleotides with up to six non-nucleotide bridges between purines were synthesized and their ability to bind ATP, cAMP or FAD was measured. Triplex motifs with several single-nucleotide binding sites were found to bind purines more tightly than triplexes with one large binding site. The optimized triplex consists of 59 residues and four C3-bridges. It can bind up to four equivalents of ligand with apparent Kd values of 52 µM for ATP, 9 µM for FAD, and 2 µM for cAMP. An immobilized version fuels bioluminescence via release of ATP at body temperature. These results show that motifs for high-density capture, storage and release of energy-rich biomolecules can be constructed from synthetic DNA.

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“…Another class of binding motifs are based on rational design, for example by using canonical structures, such as duplexes and triplexes that contain nucleotide or nucleobase gaps as binding sites. This class of binders includes DNA duplexes with abasic sites that can bind larger aromatic ligands and modified DNA triplexes that act as sensors or receptors for nucleobases. Triplexes with a single‐nucleotide gap in the oligopurine segment have been shown to bind purine nucleotides with low micromolar affinity .…”

Section: Introductionmentioning

confidence: 99%

Noncovalent Spin‐Labeling of DNA and RNA Triplexes

Kamble

Wolfrum

Halbritter

et al. 2020

Chemistry & Biodiversity

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Studying nucleic acids often requires labeling. Many labeling approaches require covalent bonds between the nucleic acid and the label, which complicates experimental procedures. Noncovalent labeling avoids the need for highly specific reagents and reaction conditions, and the effort of purifying bioconjugates. Among the least invasive techniques for studying biomacromolecules are NMR and EPR. Here, we report noncovalent labeling of DNA and RNA triplexes with spin labels that are nucleobase derivatives. Spectroscopic signals indicating strong binding were detected in EPR experiments in the cold, and filtration assays showed micromolar dissociation constants for complexes between a guanine‐derived label and triplex motifs containing a single‐nucleotide gap in the oligopurine strand. The advantages and challenges of noncovalent labeling via this approach that complements techniques relying on covalent links are discussed.

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Tuning the selectivity of triplex DNA receptors

Abstract: Effects of hydrogen bonding clamps on the selectivity of triplex DNA receptors were studied. Incorporation of a 5-methyl-2-thiocytosine base to the parallel homopyrimidine region of a triplex receptor enabled selective molecular recognition of an inosine ligand.

Cited by 10 publications

References 28 publications

Effect of preorganization on the affinity of synthetic DNA binding motifs for nucleotide ligands

Effect of preorganization on the affinity of synthetic DNA binding motifs for nucleotide ligands

DNA Triplexes That Bind Several Cofactor Molecules

Noncovalent Spin‐Labeling of DNA and RNA Triplexes

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