Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Ligand Binding to DNA and RNA

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 23402

Share This Special Issue

Special Issue Editor

Dr. Marijana Radić Stojković

E-Mail Website
Guest Editor

Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
Interests: supramolecular chemistry; DNA, RNA, molecular recognition; spectroscopy; heterocyclic chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

The scientific interest in DNA and RNA and their biological activity has not subside over 50 years. Due to their functions (replication, transcriptional and translational regulation, enzymatic reactions), DNA and, on a growing scale, RNA macromolecules are the molecular targets of many drugs that are used in cancer therapy. Small molecules that form non-covalent supramolecular complexes with DNA or RNA could influence biochemical processes in living cells. For example, small-molecule complexation could inhibit the replication of DNA and its transcription to RNA and inhibit DNA–protein interactions. Therefore, the biological activity of numerous small molecules often directly depends on their interactions with DNA or RNA, although small-molecule cytotoxicity is also linked to metabolic pathways and their transport through the cell membrane.

Nucleic acids can be recognized by a small molecule (ligand) through base readout (recognition of unique chemical signatures of DNA bases) and shape readout (when the ligand recognizes a sequence-dependent DNA shape).

Nucleic acid structures present a wide variety of shapes with varying major and minor groove widths that can be recognized by small molecules by means of non-specific (mainly electrostatic) binding on the nucleic acid exterior and specific groove binding and intercalation (insertion of planar aromatic molecules between base pairs). DNA–RNA hybrid and multistranded structures are formed as intermediate structures during many biologically important processes such as DNA replication and transcription, telomere replication, and replication of HIV. Also, since telomerase activity can be inhibited through the binding of ligands either to DNA–RNA hybrids or to G-quadruplex structures, it is essential to study ligands’ interactions with both targets.

The design and synthesis of small molecules that could selectively recognize and bind specific sequences and/or specific DNA/RNA structural patterns (for example, single-stranded structures, DNA–RNA hybrids, triple helices, G-quadruplexes) and signal their binding by specific response (for example, by an increase or decrease of a spectroscopic answer) is a great challenge for chemists.

Dr. Marijana Radić Stojković
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

DNA/RNA recognition
small organic molecule
non-covalent supramolecular complex
G-quadruplex
DNA–RNA hybrid
triple helix

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

22 pages, 9737 KiB

Open AccessArticle

Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding

by Silvija Maračić, Petra Grbčić, Suresh Shammugam, Marijana Radić Stojković, Krešimir Pavelić, Mirela Sedić, Sandra Kraljević Pavelić and Silvana Raić-Malić

Molecules 2021, 26(22), 7060; https://doi.org/10.3390/molecules26227060 - 22 Nov 2021

Cited by 3 | Viewed by 2815

Abstract

The novel 1,2,3-triazolyl-appended N- and O-heterocycles containing amidine 4–11 and amidoxime 12–22 moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine 5 and coumarine amidine 11 had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC₅₀ values in the nM range. Although compound 5 was toxic to non-tumor HFF cells, compound 11 showed certain selectivity. From the amidoxime series, quinoline amidoximes 18 and 20 showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound 20 that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds 5 and 10 most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds 6, 9 and 11 bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Figure 1

14 pages, 4139 KiB

Open AccessArticle

Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region

by Peter Jonas Wickhorst, Heiko Ihmels and Thomas Paululat

Molecules 2021, 26(21), 6595; https://doi.org/10.3390/molecules26216595 - 30 Oct 2021

Cited by 1 | Viewed by 1548

Abstract

Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biological activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence a2 with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium (1), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of a2 with four stacked guanine quartets. Furthermore, ligand 1 has high affinity toward a2 and binds by terminal π stacking to the G1–G11–G15–G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of a2. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Graphical abstract

14 pages, 3700 KiB

Open AccessArticle

Examining the Effects of Netropsin on the Curvature of DNA A-Tracts Using Electrophoresis

by Jillian Miller and Justin P. Peters

Molecules 2021, 26(19), 5871; https://doi.org/10.3390/molecules26195871 - 28 Sep 2021

Viewed by 1897

Abstract

A-tracts are sequences of repeated adenine bases that, under the proper conditions, are capable of mediating DNA curvature. A-tracts occur naturally in the regulatory regions of many organisms, yet their biological functions are not fully understood. Orienting multiple A-tracts together constructively or destructively in a phase has the potential to create different shapes in the DNA helix axis. One means of detecting these molecular shape differences is from altered DNA mobilities measured using electrophoresis. The small molecule netropsin binds the minor groove of DNA, particularly at AT-rich sequences including A-tracts. Here, we systematically test the hypothesis that netropsin binding eliminates the curvature of A-tracts by measuring the electrophoretic mobilities of seven 98-base pair DNA samples containing different numbers and arrangements of centrally located A-tracts under varying conditions with netropsin. We find that netropsin binding eliminates the mobility difference between the DNA fragments with different A-tract arrangements in a concentration-dependent manner. This work provides evidence for the straightening of A-tracts upon netropsin binding and illustrates an artificial approach to re-sculpt DNA shape. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Graphical abstract

21 pages, 2556 KiB

Open AccessArticle

Biological Activity of Newly Synthesized Benzimidazole and Benzothizole 2,5-Disubstituted Furane Derivatives

by Livio Racané, Ivo Zlatar, Nataša Perin, Maja Cindrić, Vedrana Radovanović, Mihailo Banjanac, Suresh Shanmugam, Marijana Radić Stojković, Karmen Brajša and Marijana Hranjec

Molecules 2021, 26(16), 4935; https://doi.org/10.3390/molecules26164935 - 14 Aug 2021

Cited by 14 | Viewed by 2870

Abstract

Newly designed and synthesized cyano, amidino and acrylonitrile 2,5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity. For potential antitumor activity, the compounds were tested in 2D and 3D cell culture methods on three human lung cancer cell lines, A549, HCC827 and NCI-H358, with MTS cytotoxicity and BrdU proliferation assays in vitro. Compounds 5, 6, 8, 9 and 15 have been proven to be compounds with potential antitumor activity with high potential to stop the proliferation of cells. In general, benzothiazole derivatives were more active in comparison to benzimidazole derivatives. Antimicrobial activity was evaluated with Broth microdilution testing (according to CLSI (Clinical Laboratory Standards Institute) guidelines) on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, Saccharomyces cerevisiae was included in testing as a eukaryotic model organism. Compounds 5, 6, 8, 9 and 15 showed the most promising antibacterial activity. In general, the compounds showed antitumor activity, higher in 2D assays in comparison with 3D assays, on all three cell lines in both assays. In natural conditions, compounds with such an activity profile (less toxic but still effective against tumor growth) could be promising new antitumor drugs. Some of the tested compounds showed antimicrobial activity. In contrast to ctDNA, the presence of nitro group or chlorine in selected furane-benzothiazole structures did not influence the binding mode with AT-DNA. All compounds dominantly bound inside the minor groove of AT-DNA either in form of monomers or dimer and higher-order aggregates. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Figure 1

15 pages, 2948 KiB

Open AccessArticle

Ditopic Aza-Scorpiand Ligands Interact Selectively with ds-RNA and Modulate the Interaction upon Formation of Zn²⁺ Complexes

by Lluís Guijarro, Álvaro Martínez-Camarena, Javier U. Chicote, Antonio García-España, Enrique García-España, Mario Inclán, Begoña Verdejo and Jorge González-García

Molecules 2021, 26(13), 3957; https://doi.org/10.3390/molecules26133957 - 28 Jun 2021

Cited by 1 | Viewed by 1713

Abstract

Nucleic acids are essential biomolecules in living systems and represent one of the main targets of chemists, biophysics, biologists, and nanotechnologists. New small molecules are continuously developed to target the duplex (ds) structure of DNA and, most recently, RNA to be used as therapeutics and/or biological tools. Stimuli-triggered systems can promote and hamper the interaction to biomolecules through external stimuli such as light and metal coordination. In this work, we report on the interaction with ds-DNA and ds-RNA of two aza-macrocycles able to coordinate Zn²⁺ metal ions and form binuclear complexes. The interaction of the aza-macrocycles and the Zn²⁺ metal complexes with duplex DNA and RNA was studied using UV thermal and fluorescence indicator displacement assays in combination with theoretical studies. Both ligands show a high affinity for ds-DNA/RNA and selectivity for ds-RNA. The ability to interact with these duplexes is blocked upon Zn²⁺ coordination, which was confirmed by the low variation in the melting temperature and poor displacement of the fluorescent dye from the ds-DNA/RNA. Cell viability assays show a decrease in the cytotoxicity of the metal complexes in comparison with the free ligands, which can be associated with the observed binding to the nucleic acids. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Figure 1

8 pages, 4960 KiB

Open AccessArticle

Two Intercalation Mechanisms of Oxazole Yellow Dimer (YOYO-1) into DNA

by Karolina Kucharska, Marta Pilz, Krzysztof Bielec, Tomasz Kalwarczyk, Patrycja Kuźma and Robert Hołyst

Molecules 2021, 26(12), 3748; https://doi.org/10.3390/molecules26123748 - 19 Jun 2021

Cited by 1 | Viewed by 3506

Abstract

The oxazole yellow dye, YOYO-1 (a symmetric homodimer), is a commonly used molecule for staining DNA. We applied the brightness analysis to study the intercalation of YOYO-1 into the DNA. We distinguished two binding modes of the dye to dsDNA: mono-intercalation and bis-intercalation. Bis-intercalation consists of two consecutive mono-intercalation steps, characterised by two distinct equilibrium constants (with the average number of base pair per binding site equals 3.5):

K_{1} = 3.36 \pm 0.43 \times 10^{7} M^{- 1}

and

K_{2} = 1.90 \pm 0.61 \times 10^{5} M^{- 1}

, respectively. Mono-intercalation dominates at high concentrations of YOYO-1. Bis-intercalation occurs at low concentrations. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Graphical abstract

Review

Jump to: Research

17 pages, 2238 KiB

Open AccessReview

DNA Dyes—Highly Sensitive Reporters of Cell Quantification: Comparison with Other Cell Quantification Methods

by Anna Ligasová and Karel Koberna

Molecules 2021, 26(18), 5515; https://doi.org/10.3390/molecules26185515 - 11 Sep 2021

Cited by 8 | Viewed by 8006

Abstract

Cell quantification is widely used both in basic and applied research. A typical example of its use is drug discovery research. Presently, plenty of methods for cell quantification are available. In this review, the basic techniques used for cell quantification, with a special emphasis on techniques based on fluorescent DNA dyes, are described. The main aim of this review is to guide readers through the possibilities of cell quantification with various methods and to show the strengths and weaknesses of these methods, especially with respect to their sensitivity, accuracy, and length. As these methods are frequently accompanied by an analysis of cell proliferation and cell viability, some of these approaches are also described. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Ligand Binding to DNA and RNA

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI