Soft-Surface DNA Nanotechnology: DNA Constructs Anchored and Aligned to Lipid Membrane**

No strings attached: At least three attachment points are needed to align a two-dimensional DNA nanoconstruct to a soft lipid membrane surface with a porphyrin nucleoside as membrane anchor (see picture). The resulting freely diffusing DNA constructs can be reversibly assembled on the surface thus enabling the possibility of a self-repairing system. \ua9 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Self-Assembled Nanoscale DNA–Porphyrin Complex for Artificial Light Harvesting

Mimicking green plants’ and bacteria’s extraordinary ability to absorb a vast number of photons and harness their energy is a longstanding goal in artificial photosynthesis. Resonance energy transfer among donor dyes has been shown to play a crucial role on the overall transfer of energy in the natural systems. Here, we present artificial, self-assembled, light-harvesting complexes consisting of DNA scaffolds, intercalated YO-PRO-1 (YO) donor dyes and a porphyrin acceptor anchored to a lipid bilayer, conceptually mimicking the natural light-harvesting systems. A model system consisting of 39-mer duplex DNA in a linear wire configuration with the porphyrin attached in the middle of the wire is primarily investigated. Utilizing intercalated donor fluorophores to sensitize the excitation of the porphyrin acceptor, we obtain an effective absorption coefficient 12 times larger than for direct excitation of the porphyrin. On the basis of steady-state and time-resolved emission measurements and Markov chain simulations, we show that YO-to-YO resonance energy transfer substantially contributes to the overall flow of energy to the porphyrin. This increase is explained through energy migration along the wire allowing the excited state energy to transfer to positions closer to the porphyrin. The versatility of DNA as a structural material is demonstrated through the construction of a more complex, hexagonal, light-harvesting scaffold yielding further increase in the effective absorption coefficient. Our results show that, by using DNA as a scaffold, we are able to arrange chromophores on a nanometer scale and in this way facilitate the assembly of efficient light-harvesting systems

Reversible Hybridization of DNA Anchored to a Lipid Membrane via Porphyrin

The binding of zinc–porphyrin-anchored linear DNA to supported lipid membranes was studied using quartz crystal microbalance with dissipation monitoring (QCM-D). The hydrophobic anchor is positioned at the ninth base of 39-base-pair-long DNA sequences, ensuring that the DNA is positioned parallel to the membrane surface when bound, an important prerequisite for using this type of construct for the creation of two-dimensional (2D) DNA patterns on the surface. The anchor consists of a porphyrin group linked to the DNA via two or three phenylethynylene moieties. Double-stranded DNA where one of the strands was modified with either of these anchors displayed irreversible binding, although binding to the membrane was faster for the derivatives with the short anchor. The binding and subsequent hybridization of single-stranded constructs on the surface was demonstrated at 60 °C, for both anchors, revealing a coverage-dependent behavior. At low coverage, hybridization results in an increase in mass (as measured by QCM-D) by a factor of ∼1.5, accompanied by a slight increase in the rigidity of the DNA layer. At high coverage, hybridization expels molecules from the membrane, associated with an initial increase, followed by a decrease in DNA mass (as detected both by QCM-D and by an optical technique). Melting of the DNA on the surface was performed, followed by rehybridization of the single-stranded species left on the surface with their complementary strand, demonstrating the reversibility inherent in using DNA for the formation of membrane-confined nanopatterns

Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315

IDH1 plays a critical role in a number of metabolic processes and serves as a key source of cytosolic NADPH under conditions of cellular stress. However, few inhibitors of wild-type IDH1 have been reported. Here we present the discovery and biochemical characterization of two novel inhibitors of wild-type IDH1. In addition, we present the first ligand-bound crystallographic characterization of these novel small molecule IDH1 binding pockets. Importantly, the NADPH competitive α,β-unsaturated enone <b>1</b> makes a unique covalent linkage through active site H315. As few small molecules have been shown to covalently react with histidine residues, these data support the potential utility of an underutilized strategy for reversible covalent small molecule design

Novel Modes of Inhibition of Wild-Type Isocitrate Dehydrogenase 1 (IDH1): Direct Covalent Modification of His315

IDH1 plays a critical role in a number of metabolic processes and serves as a key source of cytosolic NADPH under conditions of cellular stress. However, few inhibitors of wild-type IDH1 have been reported. Here we present the discovery and biochemical characterization of two novel inhibitors of wild-type IDH1. In addition, we present the first ligand-bound crystallographic characterization of these novel small molecule IDH1 binding pockets. Importantly, the NADPH competitive α,β-unsaturated enone <b>1</b> makes a unique covalent linkage through active site H315. As few small molecules have been shown to covalently react with histidine residues, these data support the potential utility of an underutilized strategy for reversible covalent small molecule design