The unprecedented use of anthracene photodimerization within a protein or peptide system is explored through its incorporation into a DNA-binding peptide, derived from the GCN4 transcription factor. This study demonstrates an effective and dynamic interplay between a photoreaction and a peptide-DNA assembly, with each process able to exert control over the other.
The reversible photocontrol of an enzyme governing blood coagulation is demonstrated. The thrombin binding aptamer (TBA), was rendered photochromic by modification with two anthracene groups. Lighttriggered anthracene photodimerisation distorts its structure, inhibiting binding of the enzyme thrombin, which in turn triggers catalysis and the resulting clotting process.External control of biomolecule function is important for regulating biological processes that are relevant to various therapeutic and diagnostic applications. Photoregulation is a popular method of control due to the high level of specificity gained without the use of additional chemical reagents, 1 with photoswitchable groups allowing properties to be controlled in a reversible manner. As part of ongoing interest in this area, there are now a number of examples of different photoactive groups used for photocontrollable catalysis. 1a,2,3 Here, through the use of a photoswitchable DNA aptamer that displays anthracene photochromism, we demonstrate a new way of using light to reversibly control a catalytic process.Human a-thrombin, an enzyme from the family of serine proteases, is a key biological protein involved in the process of blood coagulation at the site of a blood vessel injury. 4 It has two anion binding exosites, one of which (exosite I) binds fibrinogen. During the formation of a blood clot, thrombin catalyses the production of insoluble fibrin polymers from soluble fibrinogen monomers. DNA aptamers, short single stranded oligonucleotides generated synthetically to bind proteins and small molecules, are widely used for a range of applications linked to diagnostics and therapy. 5 The thrombin binding aptamer or TBA (Fig. 1) is a 15-mer that adopts an anti-parallel G-quadruplex (G4) tertiary structure in the presence of K + ions and binds to thrombin at exosite I, the fibrinogen binding site. 6,7 The resulting complex competitively inhibits the binding of the enzyme to fibrinogen, thereby inhibiting the process of blood coagulation. This has led to the consideration of TBA and related compounds as treatments for medical conditions linked to blood clotting disorders. 5d However the use of anticoagulants, including traditional ones (e.g. heparin or warfarin), can often result in other healthcare risks. 8 For example, the reduction in systemic clotting capability could mean that wound healing is compromised at injury sites away from where anticoagulation is required. A dynamic system in which anticoagulation could be deactivated locally using an orthogonal and external source, and more quickly than the body's clearance systems, could provide an effective solution to such an issue.Previous examples exploring this idea using TBA derivatives 2d, f,7b have included azobenzene 2d and nitrophenyl 2f systems in which the application of light was found to alter clotting times. Anthracene photochromism is known to be particularly effective in photoregulatory processes within supramolecular systems as its reversible photodimerisation reaction can induce s...
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