Synthesis of chemically modified DNA

Naturally occurring DNA is encoded by the four nucleobases adenine, cytosine, guanine and thymine. Yet minor chemical modifications to these bases, such as methylation, can significantly alter DNA function, and more drastic changes, such as replacement with unnatural base pairs, could expand its function. In order to realize the full potential of DNA in therapeutic and synthetic biology applications, our ability to ‘write’ long modified DNA in a controlled manner must be improved. This review highlights methods currently used for the synthesis of moderately long chemically modified nucleic acids (up to 1000 bp), their limitations and areas for future expansion.

Download Full-text

Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry

Biomedicines ◽

10.3390/biomedicines9060628 ◽

2021 ◽

Vol 9 (6) ◽

pp. 628

Author(s):

Dagmara Baraniak ◽

Jerzy Boryski

Keyword(s):

Nucleic Acids ◽

State Of The Art ◽

Modified Oligonucleotides ◽

Synthetic Genes ◽

Chemically Modified ◽

Amide Linkage ◽

Dna And Rna ◽

Modified Dna ◽

Modified Nucleic Acids ◽

Non Coding Rnas

This review covers studies which exploit triazole-modified nucleic acids in the range of chemistry and biology to medicine. The 1,2,3-triazole unit, which is obtained via click chemistry approach, shows valuable and unique properties. For example, it does not occur in nature, constitutes an additional pharmacophore with attractive properties being resistant to hydrolysis and other reactions at physiological pH, exhibits biological activity (i.e., antibacterial, antitumor, and antiviral), and can be considered as a rigid mimetic of amide linkage. Herein, it is presented a whole area of useful artificial compounds, from the clickable monomers and dimers to modified oligonucleotides, in the field of nucleic acids sciences. Such modifications of internucleotide linkages are designed to increase the hybridization binding affinity toward native DNA or RNA, to enhance resistance to nucleases, and to improve ability to penetrate cell membranes. The insertion of an artificial backbone is used for understanding effects of chemically modified oligonucleotides, and their potential usefulness in therapeutic applications. We describe the state-of-the-art knowledge on their implications for synthetic genes and other large modified DNA and RNA constructs including non-coding RNAs.

Download Full-text

RNA Chemistry for RNA Biology

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2019.368 ◽

2019 ◽

Vol 73 (5) ◽

pp. 368-373 ◽

Cited By ~ 2

Author(s):

Pascal Röthlisberger ◽

Christian Berk ◽

Jonathan Hall

Keyword(s):

Chemical Synthesis ◽

Nucleic Acids ◽

Chemical Biology ◽

Rna Synthesis ◽

Intrinsic Properties ◽

Chemical Modifications ◽

Chemically Modified ◽

Wide Range ◽

Rna Biology ◽

Modified Nucleic Acids

Advances in the chemical synthesis of RNA have opened new possibilities to address current questions in RNA biology. Access to site-specifically modified oligoribonucleotides is often a pre-requisite for RNA chemical-biology projects. Driven by the enormous research efforts for development of oligonucleotide therapeutics, a wide range of chemical modifications have been developed to modulate the intrinsic properties of nucleic acids in order to fit their use as therapeutics or research tools. The RNA synthesis platform, supported by the NCCR RNA & Disease, aims to provide access to a large variety of chemically modified nucleic acids. In this review, we describe some of the recent projects that involved work of the platform and highlight how RNA chemistry supports new discoveries in RNA biology.

Download Full-text

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Genes ◽

10.3390/genes13010046 ◽

2021 ◽

Vol 13 (1) ◽

pp. 46

Author(s):

Yuliya Dantsu ◽

Ying Zhang ◽

Wen Zhang

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Tertiary Structures ◽

Chemically Modified ◽

Naturally Occurring ◽

Modified Dna ◽

Target Binding ◽

Oligonucleotide Analogues ◽

Drug Delivery Devices

Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.

Download Full-text

Transcription of 4′-thioDNA templates to natural RNA in vitro and in mammalian cells

Chemical Communications ◽

10.1039/c4cc08862j ◽

2015 ◽

Vol 51 (37) ◽

pp. 7887-7890 ◽

Cited By ~ 17

Author(s):

Hideto Maruyama ◽

Kazuhiro Furukawa ◽

Hiroyuki Kamiya ◽

Noriaki Minakawa ◽

Akira Matsuda

Keyword(s):

Nucleic Acids ◽

Mammalian Cells ◽

Genetic Material ◽

Rna Polymerases ◽

Chemically Modified ◽

Biological Studies ◽

Modified Nucleic Acids

Synthetic chemically modified nucleic acids, which are compatible with DNA/RNA polymerases, have great potential as a genetic material for synthetic biological studies.

Download Full-text

Chemically modified nucleic acids as immunodetectable probes in hybridization experiments.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.81.11.3466 ◽

1984 ◽

Vol 81 (11) ◽

pp. 3466-3470 ◽

Cited By ~ 104

Author(s):

P. Tchen ◽

R. P. Fuchs ◽

E. Sage ◽

M. Leng

Keyword(s):

Nucleic Acids ◽

Chemically Modified ◽

Modified Nucleic Acids

Download Full-text

Nuclease stability of boron-modified nucleic acids: application to label-free mismatch detection

Organic & Biomolecular Chemistry ◽

10.1039/c5ob01815c ◽

2015 ◽

Vol 13 (43) ◽

pp. 10604-10608 ◽

Cited By ~ 5

Author(s):

Maëva Reverte ◽

Jean-Jacques Vasseur ◽

Michael Smietana

Keyword(s):

Nucleic Acids ◽

Boronic Acid ◽

Enzymatic Degradation ◽

Label Free ◽

New Class ◽

Mismatch Detection ◽

Modified Dna ◽

Modified Nucleic Acids

Boronic acid modified DNA emerged as a new class of resistant oligonucleotides against enzymatic degradation. This property has been used to develop an enzyme-assisted label free method for mismatch detection.

Download Full-text

Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries

Journal of Nucleic Acids ◽

10.1155/2012/156482 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Yuuya Kasahara ◽

Masayasu Kuwahara

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Biological Research ◽

Future Research ◽

Chemical Modifications ◽

Additional Time ◽

Nucleotide Analogs ◽

Enzymatic Production ◽

Chemically Modified ◽

Nucleic Acid Aptamers

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Download Full-text