Special Issue "Nucleic Acids"

Guest Editor
Prof. Dr. Per H.J. Carlsen
Department of Chemistry, Norwegian University of Science and Technology, N-7491 Trondheim, Norway
E-mail:

Nucleic Acids, Nucleosides, Nucleotides, Polynucleotides

Manuscript ID: molecules-nuclacids-20081006-jp-Mizushina
Title:DNA Polymerase b Inhibition by Kohamaic Acid A Derivatives
Authors: Yoshiyuki Mizushina ^1,2,*, Toshifumi Takeuchi ³, Fumio Sugawara ³, Yuko Kumamoto-Yonezawa ¹, Masaharu Takemura ⁴, Mitsuru Sasaki ⁵, Hiromi Yoshida ^1,2, and Hirosato Takikawa ⁵
Affiliations: ¹ Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan
² Cooperative Research Center of Life Sciences, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan
³ Department of Applied Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan
⁴ Faculty of Science, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601, Japan
⁵ Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan
*Corresponding author: Yoshiyuki Mizushina, Tel: +81-78-974-1551 (Ext. 3232); Fax: +81-78-974-5689; E-mail: mizushin@nutr.kobegakuin.ac.jp
Abstract: We previously isolated a novel natural product, designated kohamaic acid A (KA-A), as an inhibitor of the first cleavage of fertilized sea urchin eggs, and found that this compound could selectively inhibit the activities of mammalian DNA polymerases (pols). In this paper, we chemically synthesized the 11 derivatives of KA-A, such as the straight-chain analogue and its chain-elongated derivatives, and the pol inhibitory activity of the some chain-elongated derivatives were stronger than that of KA-A (IC₅₀ values for pols a and b were 4.2 and 5.5 mM, respectively); therefore, the length of the side chain group of KA-A is important for the pol inhibition. KA-A derivatives could prevent human cancer cell (promyelocytic leukemia cell line, HL-60) growth as same tendency as the inhibition of mammalian pols. Since pol b is the smallest, we used it to analyze the biochemical relationship with KA-A derivatives. Biochemical, BIAcore and computer modeling analyses demonstrated that these compounds bound selectively to the N-terminal 8 kDa domain of pol b, and KA-A derivatives inhibited the DNA template binding activity. The relationship between the three-dimensional molecular structure of KA-A related compounds and these inhibitory activities is discussed.
Keywords: kohamaic acid A (KA-A), DNA polymerase (DNA-directed DNA polymerase [E.C. 2.7.7.7], pol), enzyme inhibitor, cytotoxicity, computer simulation.

Manuscript ID: molecules-nuclacids-20081009-ru-Yevdokimov
Type of Paper: Review
Title: From Liquid-Crystalline Dispersions to “Rigid” DNA Nanoconstructions
Authors: Yu. M. Yevdokimov et al.
Affiliation: Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Moscow, 119991, Vavilova str.32, Russia
E-mail: yevdokim@eimb.ru
Abstract: The review describes the formation and the physico-chemical properties of the liquid-crystalline dispersions of the double-stranded nucleic acids (DNA, RNA) obtained as a result of the phase exclusion of these molecules from water-salt polymer-containing solutions. The fundamental data that reflect the behavior of these biopolymeric molecules in the quasinematic layers of particles of the cholesteric liquid-crystalline dispersions were used as a background for creation of the DNA nanoconstructions, containing different “guest” (biologically active or/and chemical substances) molecules of practical importance. Two theoretically possible ways for transition from “liquid” state of the DNA molecules in dispersions to rigid nanoconstructions formed by DNA molecules are considered. The first way is based on linking the neighboring DNA molecules fixed in the structure of quasinematic layers with “nanobridges” consisting of alternating antibiotic molecules and metal ions. The second way is based on local modification of the DNA secondary structure, induced by treatment of dispersions with rare-earth cations, accompanied both by amplification of DNA-DNA interaction and a strong decrease in solubility of these molecules. The unique properties of the formed rigid DNA nanoconstructions dictating the scope of their practical application are outlined and a few examples here are given.

Manuscript ID: molecules-nuclacids-20081016-cn-Zeng
Type of Paper: Article
Title: Effects of Pulsed Electric Field on DNA degradation and leakage from E.coli and S. cerevisiae Cell
Authors: Ying Zhang and Xin An Zeng*
Affiliation: College of Light Industry and Food Science, South China University of Technology, Guangzhou 510640, Guangdong, China
Email: xazeng@scut.edu.cn
Abstract: High intensity pulsed electric field (PEF) is one of the most potential industrialized non-thermal sterilization technologies. Meanwhile, its mechanism remains unclear up to now. This paper focuses on studying the influence of PEF treatments on DNA molecules in suspending E. coli and S. cerevisiae cells. It was demonstrated from ultraviolet spectrophotometric analysis that the amount of leaked protein and nucleic acid increased with applied PEF strength (electric field and treatment time). Furthermore, by applying ERIC-PCR and agarose gel electrophoresis analysis, it was explored that DNA molecules in both E. coli and S. cerevisiae cells were degraded to small segments under sever PEF treatment conditions (up to electric field 20 kV/cm and treatment time 539ms). As a contrast, DNA fingerprinting pictures of pasteurization treated samples showed little difference comparing to untreated ones, which demonstrated that pasteurization treatment has little effect on DNA molecules. It implies from this research that the mechanism of PEF sterilization may due to the increase of membrane permeability as well as damage of DAN molecular structure.
Keywords: pulsed electric field, non-thermal sterilization, membrane permeability, ERIC-PCR fingerprinting; DNA degradation

Manuscript ID: molecules-nuclacids-20080919-de-Starikow
Type of Paper: Review
Title: Electronic Structure of DNA: How to Construct a Correct Tight-binding Hamiltonian
Author: Jewgeni Starikow
E-mail: starikow@chemie.fu-berlin.de
Abstract: Charge transfer/transport of DNA is still a hot and controversial topic. Not only the relevant experimental data are quite disparate, but modelling of the process also experiences a number of difficulties. First - a rather large number of theoretical papers employs incorrect representation of DNA duplexes by adopting a wrong form of tight-binding Hamiltonian. This error has its roots in a several earlier papers, which are commonly cited. Second, the DNA Hamiltonians are usually endowed with inconsistent sets of parameters. The ways of improving the situation are discussed.

Manuscript ID: molecules-nuclacids-20080923-br-Neto
Title: Recently Developments in the Chemistry of Deoxyribonucleic Acid (DNA) Photointercalators: Principles, Synthesis, Applications, and Trends
Authors: Brenno A. D. Neto ^1,* and Alexandre A. M. Lapis ^1,2
Affiliations: ¹ Laboratory of Molecular Catalysis, IQ-UFRGS, Porto Alegre, RS, Brazil
² Universidade Federal do Pampa, Unipampa, Bagé, RS, Brazil
E-mail: brenno.ipi@gmail.com
Abstract: Without doubt biosensor technologies that focus on the direct detection of DNA are currently an area of tremendous interest as they play a major role in clinical, forensic and pharmaceutical applications among others. DNA photointercalators are also very useful in the study of many different disease therapy and molecular processes. In this sense, the understanding on the principles that rule this new and exciting field of research is of great importance to a rational design, synthesis and applications of new DNA photointercalators. In the present overview we will focus on the principles, synthesis, applications, and trends of recently developments in the chemistry of new DNA photointercalators.

Manuscript ID: molecules-nuclacids-20081105-pl-Robak
Type of Paper: Review
Title: Current Place of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases
Author: Tadeusz Robak
Affiliation: Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, Ciolkowskiego 2 Str., Poland
E-mail: robaktad@onet.pl
Abstract: For the last few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and became available for either in vitro studies or clinical trials. Among them an important role plays the class of antineoplastic drugs belonging to the group of purine nucleoside analogues (PNA). Three of them: pentostatin (2’-deoxycoformycin, DCF), cladribine (2-chloro-9-(2’-deoxy-β-D-arabinosyl)-adenine; 2-chloro-2’-deoxyadenosine; 2-CdA) and fludarabine (2-fluoro-9-(β-D-arabinosyl)-adenine; 2-fluoroadenosine;FA) were approved by Food and Drug Administration (FDA) for the treatment of hematological malignancies.
Recently three novel PNA: clofarabine (CAFdA), nelarabine (ara-G) and forodesine (immucillin H, BCX-1777) have been synthesized and introduced into clinical trials. This agents are useful for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies.

Manuscript ID: molecules-nuclacids-20081201-cn-Yang
Type of Paper: Review
Title: The Strategies of Get siRNA into Cells – Research Progress of Non-viral siRNA Delivery Systems
Authors: Chen Tang, Zhen-Jun Yang * and Li-He Zhang
Affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing
* Author to whom correspondence should be addressed. Tel: +86 10 82802503; E-mail: yangzj@bjmu.edu.cn.
Abstract: In recent years, small interference RNA (siRNA) and siRNA induced RNA interference (RNAi) was widely researched by scientists, hoping to bring a revolution to disease treatment. However, siRNA was not sufficiently stable and lowly efficient in getting through cell membrane. So viral and non-viral carriers were developed to deliver siRNA, and both proved to be good methods. As the non-viral carriers were safer and easier to obtain, this article will focus on the progress of its recent research.