- Toward an Artificial Oxidative DNA Photolyase
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The design, synthesis, structure, and binding affinity of two dioptic receptors for the selective molecular recognition of the cis,syn cyclobutane pyrimidine dimer are reported. The design is based on two 2,6-di(acetamino)pyridine recognition units that are covalently linked via triple bonds to an anthraquinone functional spacer unit. The convergent synthesis uses a modified Sonogashira reaction involving a zinc transmetalation as the key step. The crystal structure of one of the receptors reveals a supramolecular 1D polymer with strong interactions mediated by shape self-complementarity, π-stacking, and hydrogen bonding between adjacent molecules. Hydrogen bonding between adjacent strands enforces a parallel orientation, which leads to a noncentrosymmetric crystal structure of the highly polar compound. The receptor has an association constant of K a = 1.0 × 103 M-1 with the cis,syn pyrimidine dimer, whereas binding of the trans,syn isomer is approximately 1 order of magnitude weaker.
- Pauvert, Mickael,Laine, Patrick,Jonas, Marco,Wiest, Olaf
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- Copper(II)-directed synthesis of neutral heteroditopic [2]rotaxane ion-pair host systems incorporating hydrogen and halogen bonding anion binding cavities
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Neutral heteroditopic [2]rotaxane ion-pair host systems were synthesised via a Cu(ii) directed passive metal template strategy. Each rotaxane contains discrete, axle-separated interlocked binding sites for a guest anion and a transition metal countercatio
- Brown, Asha,Mennie, Katrina M.,Mason, Owen,White, Nicholas G.,Beer, Paul D.
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supporting information
p. 13376 - 13385
(2017/10/17)
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- Efficient formation of luminescent lanthanide(III) complexes by solid-phase synthesis and on-resin screening
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Time-resolved luminescence measurements of luminescent lanthanide complexes have advantages in biological assays and high-throughput screening, owing to their high sensitivity. In spite of the recent advances in their energy-transfer mechanism and molecular-orbital-based computational molecular design, it is still difficult to estimate the quantum yields of new luminescent lanthanide complexes. Herein, solid-phase libraries of luminescent lanthanide complexes were prepared through amide-condensation and Pd-catalyzed coupling reactions and their luminescent properties were screened with a microplate reader. Good correlation was observed between the time-resolved luminescence intensities of the solid-phase libraries and those of the corresponding complexes that were synthesized by using liquid-phase chemistry. This method enabled the rapid and efficient development of new sensitizers for SmIII, EuIII, and TbIII luminescence. Thus, solid-phase combinatorial synthesis combined with on-resin screening led to the discovery of a wide variety of luminescent sensitizers. La confidential: Solid-phase synthesis by using amide-condensation and Pd-coupling reactions enabled the efficient development of new antenna ligands for SmIII, EuIII, and Tb III atoms for discovering a wide variety of luminescent sensitizers. Copyright
- Nakamura, Tatsuya,Mizukami, Shin,Tanaka, Miho,Kikuchi, Kazuya
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p. 2685 - 2690
(2013/11/19)
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- Effects of a halogenated G-quadruplex ligand from the pyridine dicarboxamide series on the terminal sequence of XpYp telomere in HT1080 cells
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Non-canonical four-stranded structures called G-quadruplexes can form among telomere repeats during its replication. Small molecule ligands able to interact and to stabilize G-quadruplexes were shown to disrupt the binding of essential telomeric components, such as POT1 and to trigger a telomeric dysfunction associated with a delayed growth arrest in tumor cells. We describe here the chemical synthesis and the G-quadruplex binding properties of three halogenated analogs of the 360A ligand that belongs to the 2,6 pyridine dicarboxamide series. 360A is now commonly used as a benchmark both for biophysical and cellular assays as this compound was shown to display a potent affinity and selectivity for telomeric G-quadruplex DNA over duplex DNA and to induce delayed growth inhibition in HT1080 tumor cell line. Two biophysical assays indicate that, in most cases, the presence of the halogen atom seems to slightly improve the interaction with the telomeric quadruplex. For stability reasons, the bromo derivative (360A-Br) was selected for the cellular assays. Since POT1 participates to the fine tuning of the C-strand end resection during telomere replication, we investigated the effect of 360A-Br to alter the terminal nucleotide composition of XpYp telomere in HT1080 cells using C-STELA. HT1080 cells treated for up to 24 days with 360A-Br presented some minor but significant variations of C-strand terminal nucleotide composition, also observed with a partial siRNA depletion of POT1. The relevance of these minor modifications of the telomeric C-strand resection induced by 360A-Br in HT1080 cells are discussed.
- Sidibe, Assitan,Hamon, Florian,Largy, Eric,Gomez, Dennis,Teulade-Fichou, Marie-Paule,Trentesaux, Chantal,Riou, Jean-Francois
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p. 2559 - 2568
(2013/01/15)
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- Significance of interactions of BACE1-Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold
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Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1.
- Hamada, Yoshio,Ohta, Hiroko,Miyamoto, Naoko,Sarma, Diganta,Hamada, Takashi,Nakanishi, Tomoya,Yamasaki, Moe,Yamani, Abdellah,Ishiura, Shoichi,Kiso, Yoshiaki
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scheme or table
p. 2435 - 2439
(2009/12/25)
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- Concave pyridines with extended π-systems
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New 4-substituted concave pyridines 1b-d have been synthesised as precursors to allow extension of the pyridine π-system. With the Sonogashira coupling as the key synthetic step, the 4-iodo pyridine 1c was coupled with phenylacetylene (11) to give 1g in 77% yield. Because of its conjugated π system, the new concave pyridine 1g has UV absorption maxima at λmax1 = 286 nm and λmax2 = 303 nm with εmax1 = 43300 Lmol-1cm-1 and εmax2 = 39300 Lmol-1cm-1, respectively, allowing its potential application as a sensor. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Storm, Ole,Luening, Ulrich
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p. 3680 - 3685
(2007/10/03)
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