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Special Issue "Advances in Targeting Canonical and Non-canonical Nucleic Acids Structures"

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

Deadline for manuscript submissions: closed (30 June 2021).

Special Issue Editors

Dr. Angelo Spinello
E-Mail Website
Guest Editor
CNR-IOM Democritos and International School for Advanced Studies (SISSA), Trieste, Italy
Interests: molecular modeling; computer-aided drug design; molecular dynamics; QM/MM; anticancer drugs
Prof. Dr. Giampaolo Barone
E-Mail Website
Guest Editor
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Viale delle Scienze, Edificio 17, 90128 Palermo, Italy
Interests: bioinorganic chemistry; computational chemistry; electron spectroscopy; host-guest binding; transition metal chemistry
Dr. Antonio Monari
E-Mail Website
Guest Editor
University of Lorraine and CNRS, Theoretical Physics and Theoretical Chemistry Laboratory (LPCT), Nancy, France
Interests: molecular modeling and simulation; theoretical photophysics and photochemistry; time resolved spectroscopy; non-adiabatic phenomena; structural biophysics; DNA photosensitization; DNA lesions and repair mechanism; epigenetic regulations
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The maintenance of the nucleic acid structure is essential to assure the correct realization of their biological function. This includes duplication, transduction, the fine regulation of gene expression, and epigenetics. Hence, important studies dealing with the structure of isolated nucleic acids in different environments or of DNA interacting with proteins are actively performed and have allowed considerable advancements and the recognition of fine regulatory mechanisms, such as the role played by chromatin compaction in epigenetic regulations.

In addition, it is presently well recognized that under physiological conditions and in cellular environments, particular nucleic acid sequences can fold into biologically relevant “noncanonical” topologies. These peculiar structures can involve up to four nucleic acid strands, including, among others, hairpins, triplexes, G-quadruplexes, and i-motifs. Interestingly, these nucleic acid sequences are typically located within regions of the genome related to critical biological processes, such as gene regulatory sequences or telomeres, often involved in a number of human diseases, making them attractive molecular targets for drug design. Therefore, understanding the mechanistic details behind the stabilization of peculiar nucleic acid structural motifs, also due to their interaction with proteins and driving the formation of noncanonical conformations, along with their stabilization using small molecules/metal complexes, are of pivotal importance for future biomedical applications. In this regard, molecular modeling techniques (e.g., docking, extended molecular dynamics simulations, enhanced sampling methods, QM/MM calculations) are increasingly used to assist and partially rationalize experimental studies, providing the possibility to describe at the atomistic level the molecular recognition process and the structural evolution, including allosteric modulation, or to simulate important photophysical properties.

In this Special Issue, we invite the submission of short communications, original research articles, and reviews focusing on the biophysical determination and regulation of canonical and noncanonical nucleic acid/protein complexes, including, among others, histones or histon-like proteins, transcription factors, and repair and duplication enzymes. The interaction of small molecules/metal complexes with canonical/noncanonical nucleic acid structures, as well as the effect of DNA lesions on the molecular structure, will also constitute a particular focus of this issue. Moreover, research contributions combining molecular modeling along with experimental structural, photophysical, and molecular biology techniques (e.g., Cryo-EM, X-ray, UV-Vis spectroscopy, circular dichroism, FRET, fluorescence analyses, etc.) able to sinergically shed light into the drug/target binding mechanism are particularly welcomed.

Dr. Angelo Spinello
Dr. Antonio Monari
Prof. Dr. Giampaolo Barone
Guest Editors

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 papers will be 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 2000 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

  • Noncanonical DNA/RNA structures
  • DNA sensitization
  • Molecular modeling
  • Molecular recognition
  • Anticancer drugs
  • Nucleic acid/protein complexes

Published Papers (2 papers)

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Research

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Article
Electronic Circular Dichroism Spectra of DNA Quadruple Helices Studied by Molecular Dynamics Simulations and Excitonic Calculations including Charge Transfer States
Molecules 2021, 26(16), 4789; https://doi.org/10.3390/molecules26164789 - 07 Aug 2021
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Abstract
We here investigate the Electronic Circular Dichroism (ECD) Spectra of two representative Guanine-rich sequences folded in a Quadruple helix (GQ), by using a recently developed fragment diabatisation based excitonic model (FrDEx). FrDEx can include charge transfer (CT) excited states and consider the effect [...] Read more.
We here investigate the Electronic Circular Dichroism (ECD) Spectra of two representative Guanine-rich sequences folded in a Quadruple helix (GQ), by using a recently developed fragment diabatisation based excitonic model (FrDEx). FrDEx can include charge transfer (CT) excited states and consider the effect of the surrounding monomers on the local excitations (LEs). When applied to different structures generated by molecular dynamics simulations on a fragment of the human telomeric sequence (Tel21/22), FrDEx provides spectra fully consistent with the experimental one and in good agreement with that provided by quantum mechanical (QM) method used for its parametrization, i.e., TD-M05-2X. We show that the ECD spectrum is moderately sensitive to the conformation adopted by the bases of the loops and more significantly to the thermal fluctuations of the Guanine tetrads. In particular, we show how changes in the overlap of the tetrads modulate the intensity of the ECD signal. We illustrate how this correlates with changes in the character of the excitonic states at the bottom of the La and Lb bands, with larger LE and CT involvement of bases that are more closely stacked. As an additional test, we utilised FrDEx to compute the ECD spectrum of the monomeric and dimeric forms of a GQ forming sequence T30695 (5TGGGTGGGTGGGTGGG3), i.e., a system containing up to 24 Guanine bases, and demonstrated the satisfactory reproduction of the experimental and QM reference results. This study provides new insights on the effects modulating the ECD spectra of GQs and, more generally, further validates FrDEx as an effective tool to predict and assign the spectra of closely stacked multichromophore systems. Full article
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Review

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Review
New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes
Molecules 2021, 26(16), 4737; https://doi.org/10.3390/molecules26164737 - 05 Aug 2021
Cited by 1 | Viewed by 545
Abstract
This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns [...] Read more.
This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose. Full article
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