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Special Issue "Discovery, Design, Synthesis, and Application of Nucleoside/Nucleotides"

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

Deadline for manuscript submissions: 31 May 2019

Special Issue Editors

Guest Editor
Prof. Katherine L. Seley-Radtke

Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA
Website | E-Mail
Interests: nucleos(t)ides; heterocycles; drug design; enzyme inhibitors; antiviral
Co-Guest Editor
Assoc. Prof. Theodore K. Dayie

Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD, USA
Website | E-Mail
Interests: NMR; SAXS; RNA; Riboswitches; Structural Biology and Dynamics; RNA-drug interactions; Chemical-Enzymatic Labeling of Nucleotides

Special Issue Information

Dear Colleagues,

For decades, nucleosides and nucleotides have formed the cornerstone of antiviral and anticancer therapeutics. In addition, some analogues have also made progress against parasites and bacteria and in other areas. This phenomenon is a direct result of their close structural similarity to naturally occurring nucleosides. As such, any changes to their diverse scaffolds can have profound effects. In general, nucleoside and nucleotide analogues target key biological pathways in the replication cycles of many diseases; However, some have also been shown to target human enzymes, which can sometimes result in deleterious consequences. In this regard, the primary issue with this class of drugs involves selectivity. A second major issue with this class of drugs is the often-times rapid development of resistance. As a result, there is a constant need for new and more effective analogues to fight emerging and reemerging infectious diseases and cancers; thus, this Special Issue will focus on some of the leading approaches to design, synthesis, and biological investigations, as well as the various applications for this highly relevant class of compounds and their corresponding prodrugs.

Prof. Katherine Seley-Radtke
Guest Editor

Manuscript Submission Information

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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 1800 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
  • Prodrugs
  • Antiviral
  • Anticancer
  • Enzyme inhibitors

Published Papers (6 papers)

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Research

Open AccessCommunication
An Expeditious Total Synthesis of 5′-Deoxy-toyocamycin and 5′-Deoxysangivamycin
Molecules 2019, 24(4), 737; https://doi.org/10.3390/molecules24040737
Received: 4 February 2019 / Revised: 15 February 2019 / Accepted: 16 February 2019 / Published: 19 February 2019
Cited by 1 | PDF Full-text (1214 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In present paper, an expeditious total synthesis of naturally occurring 5′-deoxytoyocamycin and 5′-deoxysangivamycin was accomplished. Because of the introduction of a benzoyl group at N-6 of 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine, a Vorbrüggen glycosylation with 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose afforded a completely regioselective N-9 [...] Read more.
In present paper, an expeditious total synthesis of naturally occurring 5′-deoxytoyocamycin and 5′-deoxysangivamycin was accomplished. Because of the introduction of a benzoyl group at N-6 of 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine, a Vorbrüggen glycosylation with 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose afforded a completely regioselective N-9 glycosylation product, which is unambiguously confirmed by X-ray diffraction analysis. All of the involved intermediates were well characterized by various spectra. Full article
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Graphical abstract

Open AccessArticle
Efficient Synthesis of UDP-Furanoses via 4,5-Dicyanoimidazole(DCI)-Promoted Coupling of Furanosyl-1-Phosphates with Uridine Phosphoropiperidate
Molecules 2019, 24(4), 655; https://doi.org/10.3390/molecules24040655
Received: 18 January 2019 / Revised: 10 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
PDF Full-text (1826 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A P(V)-N activation method based on nucleoside phosphoropiperidate/DCI system has been developed for improved synthesis of diverse UDP-furanoses. The reaction conditions including temperature, amount of activator, and reaction time were optimized to alleviate the degradation of UDP-furanoses to cyclic phosphates. In addition, an [...] Read more.
A P(V)-N activation method based on nucleoside phosphoropiperidate/DCI system has been developed for improved synthesis of diverse UDP-furanoses. The reaction conditions including temperature, amount of activator, and reaction time were optimized to alleviate the degradation of UDP-furanoses to cyclic phosphates. In addition, an efficient and facile phosphoramidite route was employed for the preparation of furanosyl-1-phosphates. Full article
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Graphical abstract

Open AccessArticle
Novel Bispecific Aptamer Enhances Immune Cytotoxicity Against MUC1-Positive Tumor Cells by MUC1-CD16 Dual Targeting
Molecules 2019, 24(3), 478; https://doi.org/10.3390/molecules24030478
Received: 9 January 2019 / Revised: 25 January 2019 / Accepted: 28 January 2019 / Published: 29 January 2019
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Abstract
A promising strategy in cancer immunotherapy is the employment of a bispecific agent that can bind with both tumor markers and immunocytes for recruitment of lymphocytes to tumor sites and enhancement of anticancer immune reactions. Mucin1 (MUC1) is a tumor marker overexpressed in [...] Read more.
A promising strategy in cancer immunotherapy is the employment of a bispecific agent that can bind with both tumor markers and immunocytes for recruitment of lymphocytes to tumor sites and enhancement of anticancer immune reactions. Mucin1 (MUC1) is a tumor marker overexpressed in almost all adenocarcinomas, making it a potentially important therapeutic target. CD16 is expressed in several types of immunocytes, including NK cells, γδ-T cells, monocytes, and macrophages. In this study, we constructed the first bispecific aptamer (BBiApt) targeting both MUC1 and CD16. This aptamer consisted of two MUC1 aptamers and two CD16 aptamers linked together by three 60 nt DNA spacers. Compared with monovalent MUC1 or CD16 aptamers, BBiApt showed more potent avidity to both MUC1-positive tumor cells and CD16-positive immunocytes. Competition experiments indicated that BBiApt and monovalent aptamers bound to the same sites on the target cells. Moreover, BBiApt recruited more CD16-positive immunocytes around MUC1-positive tumor cells and enhanced the immune cytotoxicity against the tumor cells in vitro. The results suggest that, apart from bispecific antibodies, bispecific aptamers may also potentially serve as a novel strategy for targeted enhancement of antitumor immune reactions against MUC1-expressing malignancies. Full article
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Open AccessCommunication
Next Generation Sequencing-Based Molecular Marker Development: A Case Study in Betula Alnoides
Molecules 2018, 23(11), 2963; https://doi.org/10.3390/molecules23112963
Received: 30 September 2018 / Revised: 9 November 2018 / Accepted: 11 November 2018 / Published: 13 November 2018
PDF Full-text (1613 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Betula alnoides is a fast-growing valuable indigenous tree species with multiple uses in the tropical and warm subtropical regions in South-East Asia and southern China. It has been proved to be tetraploid in most parts of its distribution in China. In the present [...] Read more.
Betula alnoides is a fast-growing valuable indigenous tree species with multiple uses in the tropical and warm subtropical regions in South-East Asia and southern China. It has been proved to be tetraploid in most parts of its distribution in China. In the present study, next generation sequencing (NGS) technology was applied to develop numerous SSR markers for B. alnoides, and 64,376 contig sequences of 106,452 clean reads containing 164,357 candidate SSR loci were obtained. Among the derived SSR repeats, mono-nucleotide was the main type (77.05%), followed by di- (10.18%), tetra- (6.12%), tri- (3.56%), penta- (2.14%) and hexa-nucleotide (0.95%). The short nucleotide sequence repeats accounted for 90.79%. Among the 291 repeat motifs, AG/CT (46.33%) and AT/AT (44.15%) were the most common di-nucleotide repeats, while AAT/ATT (48.98%) was the most common tri-nucleotide repeats. A total of 2549 primer sets were designed from the identified putative SSR regions of which 900 were randomly selected for evaluation of amplification successfulness and detection of polymorphism if amplified successfully. Three hundred and ten polymorphic markers were obtained through testing with 24 individuals from B. alnoides natural forest in Jingxi County, Guangxi, China. The number of alleles (NA) of each marker ranged from 2 to 19 with a mean of 5.14. The observed (HO) and expected (HE) heterozygosities varied from 0.04 to 1.00 and 0.04 to 0.92 with their means being 0.64 and 0.57, respectively. Shannon-Wiener diversity index (I) ranged from 0.10 to 2.68 with a mean of 1.12. Cross-species transferability was further examined for 96 pairs of SSR primers randomly selected, and it was found that 48.96–84.38% of the primer pairs could successfully amplify each of six related Betula species. The obtained SSR markers can be used to study population genetics and molecular marker assisted breeding, particularly genome-wide association study of these species in the future. Full article
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Open AccessArticle
Novel 5′-Norcarbocyclic Derivatives of Bicyclic Pyrrolo- and Furano[2,3-d]Pyrimidine Nucleosides
Molecules 2018, 23(10), 2654; https://doi.org/10.3390/molecules23102654
Received: 3 September 2018 / Revised: 28 September 2018 / Accepted: 12 October 2018 / Published: 16 October 2018
PDF Full-text (1431 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Here we report the synthesis and biological activity of new 5′-norcarbocyclic derivatives of bicyclic pyrrolo- and furano[2,3-d]pyrimidines with different substituents in the heterocyclic ring. Lead compound 3i, containing 6-pentylphenyl substituent, displays inhibitory activity with respect to a number of tumor cells with [...] Read more.
Here we report the synthesis and biological activity of new 5′-norcarbocyclic derivatives of bicyclic pyrrolo- and furano[2,3-d]pyrimidines with different substituents in the heterocyclic ring. Lead compound 3i, containing 6-pentylphenyl substituent, displays inhibitory activity with respect to a number of tumor cells with a moderate selectivity index value. Compound 3i induces cell death by the apoptosis pathway with the dissipation of mitochondrial potential. Full article
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Graphical abstract

Open AccessFeature PaperArticle
2′-O-Methyl-8-methylguanosine as a Z-Form RNA Stabilizer for Structural and Functional Study of Z-RNA
Molecules 2018, 23(10), 2572; https://doi.org/10.3390/molecules23102572
Received: 5 September 2018 / Revised: 28 September 2018 / Accepted: 7 October 2018 / Published: 9 October 2018
Cited by 1 | PDF Full-text (3783 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In contrast to Z-DNA that was stabilized and well-studied for its structure by chemical approaches, the stabilization and structural study of Z-RNA remains a challenge. In this study, we developed a Z-form RNA stabilizer m8Gm, and demonstrated that incorporation of m [...] Read more.
In contrast to Z-DNA that was stabilized and well-studied for its structure by chemical approaches, the stabilization and structural study of Z-RNA remains a challenge. In this study, we developed a Z-form RNA stabilizer m8Gm, and demonstrated that incorporation of m8Gm into RNA can markedly stabilize the Z-RNA at low salt conditions. Using the m8Gm-contained Z-RNA, we determined the structure of Z-RNA and investigated the interaction of protein and Z-RNA. Full article
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Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Studies on the Molecular Mechanism of foot-and mouth disease virus-VPg (FMDV-VPg) inhibition by FUTP
Article Type: Article
Author: María‐José Camarasa

Title: Carbocyclic nucleoside analogues with an optically active norbornane fragment linked to the base by a methylen group, as an glycoside moiety
Article Type: Article
Author: Constantin Tanase
Abstract: Nucleoside analogues with a non-cyclic glycoside moiety are known as recognized antiviral drugs. Some nucleoside analogues with a cyclobutate or a cyclopentane fragment spaced from the base by a methylene group are also mentioned in the literature. In this paper we present another type of carbocyclic nucleoside analogues that contain an optically active norbornane fragment, substituted by a chlorine and a hydroxyl group, spaced to the base moiety by a methylene group.

The synthesis, characterization and preliminary screening of their antiviral activity will be described. 

 

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