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

2004 ◽  
Vol 69 (10) ◽  
pp. 1955-1970 ◽  
Author(s):  
Petr Nauš ◽  
Ivan Votruba ◽  
Michal Hocek
Keyword(s):  
Acetic Acid ◽  
Base Pair ◽  
Cross Coupling ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Base Pairs ◽  
Cross Coupling Reactions ◽  
Dna Base ◽  
Dna Base Pairs

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.

Covalent Analogues of DNA Base-Pairs and Triplets V. Synthesis of Purine-Purine and Purine-Pyrimidine Conjugates Connected by Diverse Types of Acyclic Carbon Linkages

2002 ◽  
Vol 67 (10) ◽  
pp. 1560-1578 ◽  
Author(s):  
Michal Hocek ◽  
Hana Dvořáková ◽  
Ivana Císařová
Keyword(s):  
Single Crystal ◽  
Crystal Structures ◽  
Base Pair ◽  
Cross Coupling ◽  
X Ray Diffraction ◽  
Base Pairs ◽  
X Ray ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Purine Pyrimidine

The title 1,2-bis(purin-6-yl)acetylenes, -diacetylenes, -ethylenes and -ethanes were prepared as covalent base-pair analogues starting from 6-ethynylpurines and 6-iodopurines by the Sonogashira cross-coupling or oxidative alkyne-dimerization reactions followed by hydrogenations. 6-[(1,3-Dimethyluracil-5-yl)ethynyl]purine (11) was prepared analogously and hydrogenated to the corresponding purine-pyrimidine conjugates linked via vinylene and ethylene linkers. Unlike the cytostatic bis(purin-6-yl)acetylenes and -diacetylenes, the purine-pyrimidine conjugates were inactive. Crystal structures of bis(purin-6-yl)acetylene 6a, -diacetylene 8a and -ethane 5a were determined by single-crystal X-ray diffraction.

Cytostatic 6-Arylpurine Nucleosides II. Synthesis of Sugar-Modified Derivatives: 9-(2-Deoxy-β-D-erythro-pentofuranosyl)-, 9-(5-Deoxy-β-D-ribofuranosyl)- and 9-(2,3-Dihydroxypropyl)-6-phenylpurines

2000 ◽  
Vol 65 (11) ◽  
pp. 1683-1697 ◽  
Author(s):  
Michal Hocek ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Hana Dvořáková
Keyword(s):  
Cross Coupling ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Cross Coupling Reactions ◽  
Highly Active ◽  
Phenylboronic Acids

9-(2-Deoxy-β-D-erythro-pentofuranosyl)-6-(4-substituted phenyl)purines, 9-(5-deoxy-β-D-ribofuranosyl)-6-(4-substituted phenyl)purines and 9-(2,3-dihydroxypropyl)-6-(4-substituted phenyl)purines were prepared by the Suzuki-Miyaura cross-coupling reactions of the corresponding protected 9-substituted 6-chloropurines with substituted phenylboronic acids followed by MeONa mediated deprotection. In contrast to the highly active 6-phenylpurine ribonucleosides, the title compounds did not show any considerable cytostatic activity.

scholarly journals Asymmetric base-pair opening drives helicase unwinding dynamics

2019 ◽  
Vol 116 (45) ◽  
pp. 22471-22477 ◽  
Author(s):  
Francesco Colizzi ◽  
Cibran Perez-Gonzalez ◽  
Remi Fritzen ◽  
Yaakov Levy ◽  
Malcolm F. White ◽  
...  
Keyword(s):  
Base Pair ◽  
Double Helix ◽  
The Other ◽  
Base Pairs ◽  
Dna Helicases ◽  
Cellular Processes ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Opening And Closing ◽  
Base Pair Opening

The opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.

Nonlinear Dynamics of Interconnected Structures: An Application to DNA Dynamics

2005 ◽  
Author(s):  
Amit Shukla
Keyword(s):  
Nonlinear Dynamics ◽  
Base Pair ◽  
Harmonic Excitation ◽  
Dna Dynamics ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Genetic Features ◽  
Nonlinear Potential ◽  
Single Base Pair

Nonlinear dynamics of DNA base-pairs is essential in many of the genetic features and functions of the molecule. The motion of the base-pair is influenced by the nonlinear potential between the two nucleotides as well as the adjacent base-pairs. In this paper nonlinear dynamics of the base-pairs is investigated. A single degree-of-freedom model for the base-pair dynamics as proposed by Peyrard-Bishop-Dauxois is analyzed. First a single base-pair dynamics is investigated using perturbation method. Then a three base-pair model is numerically investigated to understand the nonlinear response of the system to a harmonic excitation. Finally, it is also shown that the effect of interconnection can be minimized by selecting the environment surrounding the DNA molecule.

Transient proton transfer of base pair hydrogen bonds induced by intense terahertz radiation

2020 ◽  
Vol 22 (17) ◽  
pp. 9316-9321
Author(s):  
Kaicheng Wang ◽  
Lixia Yang ◽  
Shaomeng Wang ◽  
Lianghao Guo ◽  
Jialu Ma ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Proton Transfer ◽  
Terahertz Radiation ◽  
Base Pair ◽  
Quantum Simulation ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs

Intense terahertz radiation was applied to trigger transient proton transfer in DNA base pairs through quantum simulation.

Effect of phenolic radicals on the geometry and electronic structure of DNA base pairs: computational study

2016 ◽  
Vol 27 (10) ◽  
pp. 1650119 ◽  
Author(s):  
Mohammad Zarei ◽  
Abdolvahab Seif ◽  
Khaled Azizi ◽  
Mohanna Zarei ◽  
Jamil Bahrami
Keyword(s):  
Hydrogen Bond ◽  
Dft Calculations ◽  
Base Pair ◽  
Density Functional ◽  
Base Pairs ◽  
Water Solvent ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Phenoxy Radicals ◽  
Dna Base Pair

In this paper, we show the reaction of a hydroxyl, phenyl and phenoxy radicals with DNA base pairs by the density functional theory (DFT) calculations. The influence of solvation on the mechanism is also presented by the same DFT calculations under the continuum solvation model. The results showed that hydroxyl, phenyl and phenoxy radicals increase the length of the nearest hydrogen bond of adjacent DNA base pair which is accompanied by decrease in the length of furthest hydrogen bond of DNA base pair. Also, hydroxyl, phenyl and phenoxy radicals influenced the dihedral angle between DNA base pairs. According to the results, hydrogen bond lengths between AT and GC base pairs in water solvent are longer than vacuum. All of presented radicals influenced the structure and geometry of AT and GC base pairs, but phenoxy radical showed more influence on geometry and electronic properties of DNA base pairs compared with the phenyl and hydroxyl radicals.

scholarly journals The A·T(rWC)/A·T(H)/A·T(rH) ↔ A·T*(rwWC)/A·T*(wH)/A·T*(rwH) mutagenic tautomerization via sequential proton transfer: a QM/QTAIM study

RSC Advances ◽  
2018 ◽  
Vol 8 (24) ◽  
pp. 13433-13445 ◽  
Author(s):  
Ol'ha O. Brovarets' ◽  
Kostiantyn S. Tsiupa ◽  
Dmytro M. Hovorun
Keyword(s):  
Proton Transfer ◽  
Base Pair ◽  
Building Block ◽  
Genetic Material ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs ◽  
Self Development

We discovered tautomeric wobbling of the classical A·T DNA base pairs. This data evidence, that only a base pair with Watson–Crick architecture can be a building block of the DNA macromolecule as a genetic material, which is able for the evolutionary self-development.

Cytostatic and Antiviral 6-Arylpurine Ribonucleosides VIII. Synthesis and Evaluation of 6-Substituted Purine 3'-Deoxyribonucleosides

2006 ◽  
Vol 71 (10) ◽  
pp. 1484-1496 ◽  
Author(s):  
Michal Hocek ◽  
Peter Šilhár ◽  
Radek Pohl
Keyword(s):  
Cross Coupling ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Alkyl Aryl ◽  
Cross Coupling Reactions

A series of purine 3'-deoxyribonucleosides bearing diverse C-substituents (alkyl, aryl, hetaryl or hydroxymethyl) in the position 6 was prepared by Pd-catalyzed cross-coupling reactions of 6-iodo-9-[2,5-bis-O-(tert-butyldimethylsilyl)-3-deoxy-β-D-ribofuranosyl]purine with the corresponding organometallics followed by deprotection by (HF)3·Et3N. None of the title 3'-deoxyribonucleoside showed any cytostatic activity or anti-HCV effect in replicon assay.

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