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Biomolecules
Special Issues
Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids
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Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 8160

Special Issue Editors

Prof. Dr. Xingguo Liang

E-Mail Website
Guest Editor
1. College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
2. Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China
Interests: Z-DNA; Z-RNA; metabolism of nucleic acids; nutrition of nucleic acids; structure of nucleic acids; nucleic acids detection; circular nucleic acids; nucleic acids (nas); nanomaterials; chitosan
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Xinjing Tang

E-Mail Website
Guest Editor
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
Interests: nulceic acid drugs; gene silencing; gene editing; gene photoregulation; oligonucleotide modification
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recently, there has been a great development of science and technology for NASs (nucleic acid substances of nucleic acids, nucleotides, and nucleosides), especially highlighted by the success of mRNA vaccines. Many new functions have been discovered for nucleic acids, such as circular RNA, circular ssDNA, and lncRNA, as well as other NASs. For example, circular RNAs have been found to regulate gene expression with many interesting pathways, and some nucleosides and nucleotides have been found to encompass nutritional and healthcare functions. On the other hand, many novel understandings of the relationship between their structures and functions are proposed, especially for left-handed DNA or RNA, quadruplex, triplex, R-loop, as well as the complex between NASs and other molecules such as proteins and carbohydrates. For this Special Issue entitled “Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids”, the wide scope of research on NASs of either natural or artificially synthesized ones is welcome. We hope that these high-level research results can deepen our understanding of biomolecules and even life.

Prof. Dr. Xingguo Liang
Prof. Dr. Xinjing Tang
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 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 250 words) can be sent to the Editorial Office for assessment.

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. Biomolecules is an international peer-reviewed open access monthly 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

  • nucleosides
  • nucleotides
  • nanostructure
  • circular ssDNA
  • circular RNA
  • quadruplex
  • conjugate
  • lncRNA
  • DNAzyme
  • ribozyme

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Published Papers (3 papers)

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Research

16 pages, 1800 KB  
Article
LncRNA-Mediated miR-145 Sponging Drives FN1 and CCND1 Expression: Prognostic and Therapeutic Targets in NSCLC
by Safa Tahmasebi, Davar Amani, Babak Salimi, Ian M. Adcock and Esmaeil Mortaz
Biomolecules 2025, 15(11), 1564; https://doi.org/10.3390/biom15111564 - 6 Nov 2025
Cited by 4 | Viewed by 1090
Abstract
Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic [...] Read more.
Background: Non-small cell lung cancer (NSCLC) progression is driven by dysregulated competing endogenous RNA (ceRNA) networks, where non-coding RNAs sequester miRNAs to modulate oncogene expression. The tumor-suppressor miR-145 is frequently downregulated in NSCLC, but its lncRNA-mediated regulation remains incompletely characterized. Methods: Integrated transcriptomic analysis of NSCLC datasets (GSE135304: blood RNA from 712 patients; GSE203510: plasma miRNAs) was used to identify dysregulated genes (|log2FC| > 0.1, p < 0.05) and miRNAs (|log2FC| > 1, p < 0.05). Experimentally validated targets from miRTarBase/TarBase were intersected with dysregulated genes, followed by WikiPathways/GO enrichment. ceRNA networks were constructed via co-expression analysis. RT-qPCR validated miR-145-3p expression in A549/MRC-5 cells and NSCLC tissues. GEPIA assessed FN1/CCND1 clinical relevance. Results: We identified 8271 dysregulated genes and 52 miRNAs. miR-145-3p, critical in immune regulation, was significantly downregulated (log2FC = −1.24, p = 0.036). Intersection analysis revealed 27 miR-145-3p targets (e.g., FN1, CCND1, SMAD3) enriched in immune pathways (FDR < 0.05) and TGF-β-mediated EMT within the dysregulated geneset. Six immune-linked hub genes emerged. LncRNAs LOC729919 and LOC100134412 showed strong co-expression with hub genes and competitively bind miR-145-3p, derepressing the expression of the metastasis drivers FN1 (ECM regulator) and CCND1 (cell cycle controller). This ceRNA axis operates within a broader dysregulation of ATM-dependent DNA damage, Hippo signaling, and cell cycle pathways. RT-qPCR confirmed significant miR-145-3p suppression in NSCLC models (p < 0.05). GEPIA revealed a significant FN1-CCND1 co-expression (p = 0.0017). Conclusions: We characterize a novel LOC729919/LOC100134412–miR-145–FN1/CCND1 ceRNA axis in NSCLC pathogenesis. FN1’s prognostic value and functional linkage to CCND1 underscores its potential clinical relevance for therapeutic disruption. Full article
(This article belongs to the Special Issue Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids)
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20 pages, 3332 KB  
Article
New Benzimidazole 3′-Deoxynucleosides: Synthesis and Antiherpes Virus Properties
by Aleksandra O. Arnautova, Irina A. Aleksakhina, Ekaterina A. Zorina, Maria Ya. Berzina, Ilya V. Fateev, Barbara Z. Eletskaya, Konstantin V. Antonov, Olga S. Smirnova, Alexander S. Paramonov, Alexey L. Kayushin, Valeria L. Andronova, Georgii A. Galegov, Maria A. Kostromina, Evgeny A. Zayats, Inna L. Karpenko, Svetlana K. Kotovskaya, Valery N. Charushin, Roman S. Esipov, Anatoly I. Miroshnikov and Irina D. Konstantinova
Biomolecules 2025, 15(7), 922; https://doi.org/10.3390/biom15070922 - 23 Jun 2025
Cited by 5 | Viewed by 1252
Abstract
A series of new 3′-deoxyribosides of substituted benzimidazoles was obtained by the chemo-enzymatic method using genetically engineered E. coli purine nucleoside phosphorylase (PNP). In the case of asymmetrically substituted benzimidazole derivatives, a mixture of N1- and N3-regioisomers was formed (confirmed by NMR). The [...] Read more.
A series of new 3′-deoxyribosides of substituted benzimidazoles was obtained by the chemo-enzymatic method using genetically engineered E. coli purine nucleoside phosphorylase (PNP). In the case of asymmetrically substituted benzimidazole derivatives, a mixture of N1- and N3-regioisomers was formed (confirmed by NMR). The antiviral activity of the obtained compounds against herpes simplex virus 1 of reference strain L2 and a strain deeply resistant to acyclovir in Vero E6 cell culture was studied. 4,6-Difluoro-1-(β-D-3′-deoxyribofuranosyl)benzimidazole (IC50 = 250.92 µM, SI = 12.00) and 4,5,6-trifluoro-1-(β-D-3′-deoxyribofuranosyl)benzimidazole (IC50 = 249.96 µM, SI = 16.00) showed significant selective activity against both viral models in comparison to ribavirin (IC50 = 511.88 µM, SI > 8.00). Full article
(This article belongs to the Special Issue Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids)
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11 pages, 2808 KB  
Article
Facile Splint-Free Circularization of ssDNA with T4 DNA Ligase by Redesigning the Linear Substrate to Form an Intramolecular Dynamic Nick
by Wenhua Sun, Kunling Hu, Mengqin Liu, Jian Luo, Ran An and Xingguo Liang
Biomolecules 2024, 14(8), 1027; https://doi.org/10.3390/biom14081027 - 18 Aug 2024
Cited by 6 | Viewed by 4686
Abstract
The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to the ssDNA rings’ numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products [...] Read more.
The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to the ssDNA rings’ numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5′-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5-bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are also helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding. Full article
(This article belongs to the Special Issue Chemical Biology and Biotechnology of Nucleosides, Nucleotides, and Nucleic Acids)
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