Covalently cross-linked Watson–Crick base pair models. Part 2

Qiu, Yao Ling; Li, Hong Yu; Topalov, George; Kishi, Yoshito

doi:10.1016/s0040-4039(00)01572-0

Cited by 15 publications

(4 citation statements)

References 3 publications

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“…Structural evolution of the guanine–cytosine motif along the reaction coordinate of the cyclization process (step 2 in Figure ). The lack of conformational flexibility between the base pairs is further reinforced within a B-DNA environment, and the latter thwarts a “destacking” of the linked nucleobases. The last row illustrates the conformational freedom of the isolated base pairs, in contrast with the restriction of the accessible conformations of the product within a helical pattern.…”

Section: Resultsmentioning

confidence: 99%

What Singles Out the G[8–5]C Intrastrand DNA Cross-Link? Mechanistic and Structural Insights from Quantum Mechanics/Molecular Mechanics Simulations

et al. 2013

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Naturally occurring intrastrand oxidative cross-link lesions have proven to be a potent source of endogenous DNA damage. Among the variety of lesions that can be formed and have been identified, G[8-5]C damage (in which the C8 atom of a guanine is covalently bonded to the C5 atom of a nearby cytosine belonging to the same strand) occurs with a low incidence yet takes on special importance because of its high mutagenicity. Hybrid Car-Parrinello molecular dynamics simulations, rooted in density functional theory and coupled to molecular mechanics, have been performed to shed light on the cyclization process. The activation free energy of the reacting subsystem embedded in a solvated dodecamer is estimated to be ∼12.4 kcal/mol, which is ∼3 kcal/mol higher than the value for the prototypical G[8-5m]T lesion inferred employing the same theoretical framework [Garrec, J., Patel, C., Rothlisberger, U., and Dumont, E. (2012) J. Am. Chem. Soc.134, 2111-2119]. This study also situates the G[8-5m]mC lesion at an intermediate activation free energy (∼10.5 kcal/mol). The order of reactivity in DNA (T(•) > mC(•) > C(•)) is reversed compared to that in the reacting subsystems in the gas phase (C(•) > mC(•) > T(•)), stressing the crucial role of the solvated B-helix environment. The results of our simulations also characterize a more severe distortion for G[8-5]C than for methylene-bridged intrastrand cross-links.

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Section: Resultsmentioning

confidence: 99%

What Singles Out the G[8–5]C Intrastrand DNA Cross-Link? Mechanistic and Structural Insights from Quantum Mechanics/Molecular Mechanics Simulations

et al. 2013

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“…For experimental details of the cytostatic activity screening see 17a . Most of the compounds exhibited a cytostatic effect in micromolar range, similarly to the parent alkyl substituted model compounds 12 . Also analogously to the previous results, cytostatic potency of these compounds towards different cell lines decreased in the order CCRF-CEM > HL60 > L1210 > HeLaS3.…”

Section: Biological Activitymentioning

confidence: 89%

“…Bis(purin-6-yl)benzenes as well as (purin-6-yl)(pyrimidin-5-yl)-benzenes were prepared by double cross-coupling of phenylenebis-(stannanes) 11 . Purine dimers linked through positions 6 and 6′ with acetylene, diacetylene, vinylene and ethylene linkers were prepared 12,13 by Sonogashira cross-coupling reactions of 6-ethynylpurines with 6-halopurines or 5-iodopyrimidines or by oxidative dimerizations of ethynylpurines. Similar acetylene couplings were independently used by Matsuda 14 and Marsh 15 and alternative Heck couplings by Sessler 16 for the preparation of other types of nucleobase dimers or covalent dinucleotides that were used for self-assembly or artificial receptor studies.…”

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confidence: 99%

Covalent Analogues of DNA Base-Pairs and Triplets VII. Synthesis and Cytostatic Activity of Bis(purin-6-yl)acetylene and -diacetylene Nucleosides

Nauš

Votruba

Hocek

2004

Collect. Czech. Chem. Commun.

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The title bis(purin-6-yl)acetylene and -diacetylene nucleoside derivatives were prepared as covalent base-pair analogues starting from acyl-protected 6-ethynylpurine and 6-iodopurine nucleosides by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by deprotection. The key starting acyl-protected 6-ethynylpurine nucleosides were prepared by a sequence of cross-coupling reactions of protected 6-halopurine nucleosides with (trimethylsilyl)acetylene followed by a modified desilylation with TBAF in presence of acetic acid. Surprisingly, the acyl-protected nucleosides exhibited significant cytostatic activity higher than the fully deprotected title compounds.The effect of many clinically used antitumor agents is based on DNA cross-linking 1 or on intercalation 2 into DNA. Numerous models and analogues of Watson-Crick base pairs consisting of annelated 3 or cross-linked 4 purine and pyrimidine heterocycles or even more simple aromatic rings 5,6 have been prepared. Such base-pairs analogues may interact with DNA (e.g. by intercalation); if incorporated into single-stranded DNA, they are complementary to abasic site of a damaged DNA strand; or, alternatively, if incorporated into duplex, they form permanent cross-links.

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“…( i Pr) 2 NP(Cl)O(CH 2 ) 2 CN, Et( i Pr) 2 N, CH 2 Cl 2 , RT, 100 %; d) steps (h) 1–3, (h) 1–5, or (h) 1–7 of Scheme 1 in ref. 4b as appropriate, followed by ( i Pr) 2 NP(Cl)O(CH 2 ) 2 CN, Et( i Pr) 2 N, CH 2 Cl 2 , RT, 94 % for 2 a , 95 % for 2 b , 97 % for 2 c . Abbreviations: Bt=benzotriazol‐1‐yl, n Bu=normal butyl, DMAP=4‐dimethylaminopyridine, Et=ethyl, i Pr=isopropyl, Pyr=pyridine, TBS= tert ‐butyldimethylsilyl, TCA=trichloroacetic acid, THF=tetrahydrofuran.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of DNA Oligomers Possessing a Covalently Cross‐Linked Watson–Crick Base Pair Model

Li¹,

Qiu²,

Moyroud³

et al. 2001

Angewandte Chemie

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Covalently cross-linked Watson–Crick base pair models. Part 2

Cited by 15 publications

References 3 publications

What Singles Out the G[8–5]C Intrastrand DNA Cross-Link? Mechanistic and Structural Insights from Quantum Mechanics/Molecular Mechanics Simulations

What Singles Out the G[8–5]C Intrastrand DNA Cross-Link? Mechanistic and Structural Insights from Quantum Mechanics/Molecular Mechanics Simulations

Covalent Analogues of DNA Base-Pairs and Triplets VII. Synthesis and Cytostatic Activity of Bis(purin-6-yl)acetylene and -diacetylene Nucleosides

Synthesis of DNA Oligomers Possessing a Covalently Cross‐Linked Watson–Crick Base Pair Model

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