PNA-Based Reagents for the Direct and Site-Specific Synthesis of Thymine Dimer Lesions in Genomic DNA

Pieck, J. Carsten; Kuch, David; Grolle, Friederike; Linne, Uwe; Haas, Clemens; Carell, Thomas

doi:10.1021/ja056358i

Cited by 18 publications

(11 citation statements)

References 15 publications

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“…The obtained compounds were then alkylated with 4-(bromomethyl)acetophenone, which was prepared by radical bromination of 4-methylacetophenone ( not described ). [12] The alkylated derivatives 11a-m were isolated in moderate yields (31–56%) after 24 h at room temperature. Finally, the methyl ketone intermediates were treated with LiHMDS and reacted with diethyl oxalate to produce the α,γ –diketoesters derivatives, which were subsequently submitted to base-promoted hydrolysis (saponification) and acidification to yield the desired α,γ-diketobutanoic acids 4a-m in good yields, over two steps.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

Sari

Roy

Métifiot

et al. 2015

European Journal of Medicinal Chemistry

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The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl α,γ-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the β-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c′ exhibited an anti-HIV activity of 0.19 μM in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity.

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Section: Resultsmentioning

confidence: 99%

Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

Sari

Roy

Métifiot

et al. 2015

European Journal of Medicinal Chemistry

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“…After photon absorption, the excited FADH − in photolyase protein transfers an electron to the pyrimidine dimer lesion in the duplex DNA . As a model system, Carell et al reported a photoinduced DNA-repair reaction from a flavin donor to a thymine dimer acceptor introduced in an oligonucleotide or a defined DNA scaffold as photolyase mimics . In addition, another type of cofactor, redox-active [4Fe4S] cluster, is also found in DNA repair proteins. , Barton et al demonstrated DNA-mediated ET between the [4Fe4S] cluster in two of these proteins, MutY and endonuclease III, and the guanine radicals .…”

Section: Introductionmentioning

confidence: 99%

Photophysical and DNA-Binding Properties of Cytochrome c Modified with a Platinum(II) Complex

et al. 2010

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Cytochrome c (cyt c) derivatives modified with a platinum(II) complex at the lysine residue, cyt c(III)-[Pt(bpy)(dapap)](1) {bpy = 2,2'-bipyridine, and dapap = 3-(2,3-diaminopropionylamino)propionic acid}, have been prepared. The modified residues are Lys8, Lys13, Lys55, Lys60, Lys73, and Lys88. In the case of the cyt c(III)-[Pt(bpy)(dapap)](1) dyad, the photoexcited singlet state of (1)([Pt(bpy)(dapap)](1))* was quenched by the heme Fe(III) moiety through the intramolecular photoinduced energy-transfer reaction via a through-space mechanism. Next, in the presence of calf thymus (CT)-DNA, the DNA-responsive fluorescence properties of cyt c(III)-[Pt(bpy)(dapap)](1) isomers were investigated. The order of the obtained binding constants between the cyt c(III)-[Pt(bpy)(dapap)](1) isomer and CT-DNA in an aqueous solution suggested that the electrostatic interaction is one of the important factors to stabilize the cyt c-DNA complex. Finally, we discussed the rotational motion of the [Pt(bpy)(dapap)](2+) moiety at the surface of cyt c by fluorescence anisotropy measurement. The increase in the anisotropy parameter, r, for each cyt c isomer clearly revealed that the noncovalent recognition of the [Pt(bpy)(dapap)](2+) moiety by CT-DNA is an essential event in the formation of the cyt c-DNA complex and generation of DNA-sensitive fluorescence signals.

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“…-(Bromomethyl)acetophenone 1 was obtained as a white solid according to the published procedure[53]. Yield: 15.1 g (95%).…”

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confidence: 99%

Palladium–Carbene Complexes Supported by Polyphenylene Matrices as Catalysts for The Suzuki, Heck and cyanation reactions

Kovalev¹,

Naumkin²,

Tyurin³

et al. 2018

INEOS OPEN

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A series of N-methylimidazole ligands attached to solid matrices based on the branched polyphenylenes with 1,3,5-triphenylbenzene cores were synthesized. These macroligands readily afforded complexes of a general formula (NHC) 2 PdX 2 , which were characterized by X-ray photoelectron spectroscopy. The catalytic activities of the complexes immobilized on the polyphenylene matrices were studied in the Suzuki and Heck cross-couplings as well as cyanation of aryl halides. The results obtained indicate that they are comparable in performance to the low-molecular homogenous catalysts. The catalyst stabilities were evaluated in recycling tests which revealed that, under conditions of the coupling reactions, the suggested catalysts can be used in five cycles.Electronic supplementary information (ESI) available online: 1 H and 13 C NMR spectra of compound 3; IR spectra of compounds N-PPH-1 and 5. For ESI, see

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PNA-Based Reagents for the Direct and Site-Specific Synthesis of Thymine Dimer Lesions in Genomic DNA

Abstract: An acetophenone containing PNA-based reagent was designed for the direct and site-specific synthesis of a cis-syn thymidine dimer lesion in genomic DNA.

Cited by 18 publications

References 15 publications

Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase

Photophysical and DNA-Binding Properties of Cytochrome c Modified with a Platinum(II) Complex

Palladium–Carbene Complexes Supported by Polyphenylene Matrices as Catalysts for The Suzuki, Heck and cyanation reactions

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