Protein Recognition and Denaturation by Self‐Assembling Fragments on a DNA Quadruplex Scaffold.

Tagore, Debarati M.; Sprinz, K. Ingrid; Fletcher, Steven; Jayawickramarajah, Janarthanan; Hamilton, Andrew D.

doi:10.1002/chin.200709061

Cited by 3 publications

(5 citation statements)

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“…40 In the current manuscript, we provide new insight into how a self-assembled DNA quadruplex 2 projecting eight adamantane guest arms can assemble with porphyrin 3 to form nanowires and their networks. One rationale for using a DNA quadruplex scaffold was because the dimensions (∼1.1 nm × 1.1 nm) 43 and four fold symmetry of the porphyrin macrocycle nicely match the geometry (∼1.1 nm × 1.1 nm) 43 and four fold symmetry of a guanine quartet. Indeed, as can be seen in Figure 2c a linear nanowire should form when the self-assembling partners are properly aligned.…”

Section: Discussionmentioning

confidence: 99%

“…36–38 In addition, the adamantane moieties were specifically included since the self-assembled quadruplex 2 would then project four adamantane units from each of its two termini. Based on earlier work by our group and others on multivalent host-guest interactions on non-DNA derived supramolecular nanostructures, 39–42 we envisioned that addition of a non-covalently “cross-linking” free-base porphyrin ( 3 ) that presents four PMβ-CD hosts from each face (and has dimensions that closely match the terminal face of a DNA quadruplex) 43 should result in DNA-porphyrin array 4 as a result of repetitive multivalent host-guest interactions.…”

Section: Introductionmentioning

confidence: 99%

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Photonic DNA-Chromophore Nanowire Networks: Harnessing Multiple Supramolecular Assembly Modes

et al. 2013

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Photonic DNA nanostructures are typically prepared by the assembly of multiple sequences of long DNA strands that are conjugated covalently to various dye molecules. Herein we introduce a non-covalent method for the construction of porphyrin-containing DNA nanowires and their networks that uses the programmed assembly of a single, very short, oligodeoxyribonucleotide sequence. Specifically, our strategy exploits a number of supramolecular binding modalities (including DNA base-pairing, metal-ion coordination, and β-cyclodextrin-adamantane derived host-guest interactions) for simultaneous nanowire assembly and porphyrin incorporation. Furthermore, we also show that the resultant DNA-porphyrin assembly can be further functionalized with a complementary “off-the-shelf” DNA binding dye resulting in photonic structures with broadband absorption and energy transfer capabilities.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Photonic DNA-Chromophore Nanowire Networks: Harnessing Multiple Supramolecular Assembly Modes

et al. 2013

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“…A chemical library of 70,000 compounds has been made based on this approach, which is much smaller than most compound decks for HTS (~1,000,000 compounds). Although triplex and quadruplex DNA structures have been reported, [54][55][56] these structures are not easy to form, and decoding can be a complicated issue for these forms of DNA.…”

Section: Dna Encodingmentioning

confidence: 99%

High-Throughput Affinity-Based Technologies for Small-Molecule Drug Discovery

Zhu¹,

Cuozzo²

2009

SLAS Discovery

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High-throughput affinity-based technologies are rapidly growing in use as primary screening methods in drug discovery. In this review, their principles and applications are described and their impact on small-molecule drug discovery is evaluated. In general, these technologies can be divided into 2 groups: those that detect binding interactions by measuring changes to the protein target and those that detect bound compounds. Technologies detecting binding interactions by focusing on the protein have limited throughput but can reveal mechanistic information about the binding interaction; technologies detecting bound compounds have very high throughput, some even significantly higher than current high-throughput screening technologies, but offer limited information about the binding interaction. In addition, the appropriate use of affinity-based technologies is discussed. Finally, nanotechnology is predicted to generate a significant impact on the future of affinity-based technologies. (Journal of Biomolecular

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“…Here, we report the design, preparation, and characterization of new MR agents based on ordered and self-assembling DNA quadruplex scaffolds (19). The quadruplex-based DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) derivatives have almost 30-fold increased r 1 versus clinical Gd-chelate contrast agents and two-fold increased r 1 compared to the single oligonucleotide (ODN)-DOTA conjugate.…”

mentioning

confidence: 99%

“…Fourth, it may be possible to obtain quadruplex CAs with higher relaxivity if DOTA dendrimers with more rigid linkers can be tethered on the end of DNA quadruplex scaffold with shorter linker lengths. Lastly, functionalized DNA quadruplexes have been shown to target specific proteins (19, 29), leaving open the possibilities of functionalizing the quadruplex with fragments that target specific cells or tissues.…”

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confidence: 99%

Self-Assembling DNA Quadruplex Conjugated to MRI Contrast Agents

2009

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We report the preparation and magnetic resonance (MR) characterization of new MRI contrast agents based on gadolinium complexes conjugated to a self-assembling DNA quadruplex scaffold. As a single gadolinium-DOTA chelated DNA strand, the r 1 molar relaxivity is 6.4 mM -1 s -1 per Gd and increases to 11.7 mM -1 s -1 per Gd upon formation of a DNA quadruplex. Similar results were obtained when a gadolinium-DOTA dendrimer was conjugated to DNA, the r 1 molar relaxivity increasing to 12.9 mM -1 s -1 per Gd upon the formation of DNA quadruplex, compared to that of 6.0 mM -1 s -1 for single strand of gadolinium-DOTA dendrimer chelate. This yields an r 1 molar relaxivity of 154.8 and 46.8 mM -1 s -1 per DNA quadruplex molecular complex based on DOTA dendrimer or monomer, respectively. Importantly, the DNA quadruplex scaffold of the contrast agent is approximately 2.5 nm 3 a in size, potentially enabling this type of contrast agent to be used for targeted delivery in vivo to detect specific cells or tissues, even behind intact blood vessels.The targeted and non-invasive detection of specific pathologies in humans is a major research focus in the broad area of bioimaging sciences. To this end, magnetic resonance imaging (MRI) has emerged as an important and useful imaging strategy. As a noninvasive imaging technique, MRI provides three dimensional images of anatomic structures of living organisms at high spatial resolution (∼ 100 microns isotropic) in scan times of less than 30 minutes (1). Similar to other molecular imaging technologies, targeted MRI requires the delivery of specific probes to detect underlying biological abnormalities. Commonly used MR targeting constructs include paramagnetic liposomes (2), paramagnetic perfluorocarbon nanoparticles (3), superparamagnetic iron oxide nanoparticles (4) and small paramagnetic chelates (5). Almost always, the paramagnetic metal used is Gd 3+ because of its ability to increase the longitudinal relaxation rate (R1) of water protons and therefore to enhance the observable signal. Superparamagnetic iron oxide nanoparticles create local magnetic field distortions which increases the transverse relaxation rate (R2), effectively destroying signal and making dark contrast in images.Targeted MRI has had a major impact on the detection and treatment of cancer (6) and atherosclerosis (7). This is largely due to the accessibility of blood vessels in these diseases, as most nanoparticle formulations are on the order of 30 to >100 nm in diameter, and are too a By assuming an average distance of 3.4 Å between base-pairs, and a distance of 11 Å between adjacent guanines in each tetrad, the volume of DNA quaduplex scaffold was calculated to be 1.1 × 1.1 × 2.0 = 2.5 nm 3 .andrew.hamilton@yale.edu and erik.shapiro@yale.edu. Supporting information available: Procedures on oligonucleotides synthesis, quadruplex formation, Gd(III) ion incorporation and measurements of the relaxivities of 1X, 2X, 1Y and 2Y. This information is available free of charge via the Internet at http://pubs.acs...

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Protein Recognition and Denaturation by Self‐Assembling Fragments on a DNA Quadruplex Scaffold.

Abstract: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cited by 3 publications

References 1 publication

Photonic DNA-Chromophore Nanowire Networks: Harnessing Multiple Supramolecular Assembly Modes

Photonic DNA-Chromophore Nanowire Networks: Harnessing Multiple Supramolecular Assembly Modes

High-Throughput Affinity-Based Technologies for Small-Molecule Drug Discovery

Self-Assembling DNA Quadruplex Conjugated to MRI Contrast Agents

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