Squaramides and Ureas: A Flexible Approach to Polymerase‐Compatible Nucleic Acid Assembly

Shivalingam, Arun; Taemaitree, Lapatrada; El‐Sagheer, Afaf H.; Brown, Tom

doi:10.1002/ange.202000209

Cited by 4 publications

(6 citation statements)

References 42 publications

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“…The proposed molecular requirements also agree with our previously described model, which was derived from read-through compatibility tests of a range of backbone linkages including amides, phosphoro(di)thioates, phosphoramidates, and squaramides. 18 , 19 , 24 , 25 It is important to emphasize that the observed read-through compatibilities are dependent on the polymerase and similar polymerase dependencies were reported for other PO mimics. 18 , 19 …”

Section: Resultssupporting

confidence: 72%

“… 18 , 19 , 24 , 25 It is important to emphasize that the observed read-through compatibilities are dependent on the polymerase and similar polymerase dependencies were reported for other PO mimics. 18 , 19 …”

Section: Resultssupporting

confidence: 72%

“…In general, replication-competent artificial DNA backbones can be used for gene synthesis, 8 , 9 sequencing, 17 or nucleic acid detection. 18 A detailed study revealed several molecular characteristics of artificial backbones that are required for compatibility with DNA polymerases during replication. 19 Such polymerase compatible artificial backbones comprise 5′- S -phosphorothioesters, 20 phosphorothioates, 21 disulfides, 22 boranophosphates, 23 phosphoramidates, 10 , 24 , 25 amides, 19 , 26 ureas, 18 squaramides, 18 and triazoles.…”

Section: Introductionmentioning

confidence: 99%

“… 18 A detailed study revealed several molecular characteristics of artificial backbones that are required for compatibility with DNA polymerases during replication. 19 Such polymerase compatible artificial backbones comprise 5′- S -phosphorothioesters, 20 phosphorothioates, 21 disulfides, 22 boranophosphates, 23 phosphoramidates, 10 , 24 , 25 amides, 19 , 26 ureas, 18 squaramides, 18 and triazoles. 8 , 9 , 19 , 27 − 29 Among these, the triazole linkage (TL) represents a powerful and versatile chemical moiety that can be readily formed by the Cu I -catalyzed azide–alkyne cycloaddition (CuAAC) reaction, resulting in 1,4-disubstituted 1,2,3-triazoles.…”

Section: Introductionmentioning

confidence: 99%

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A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility

et al. 2021

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Triazole linkages (TLs) are mimics of the phosphodiester bond in oligonucleotides with applications in synthetic biology and biotechnology. Here we report the RuAAC-catalyzed synthesis of a novel 1,5-disubstituted triazole (TL 2 ) dinucleoside phosphoramidite as well as its incorporation into oligonucleotides and compare its DNA polymerase replication competency with other TL analogues. We demonstrate that TL 2 has superior replication kinetics to these analogues and is accurately replicated by polymerases. Derived structure–biocompatibility relationships show that linker length and the orientation of a hydrogen bond acceptor are critical and provide further guidance for the rational design of artificial biocompatible nucleic acid backbones.

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Section: Resultssupporting

confidence: 72%

Section: Resultssupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility

et al. 2021

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“…The RNA fragments were then ligated to become full length mRNA. This process is scalable and completely avoids the formation of dsRNA [ 53 ].…”

Section: Strategies To Improve Mrna Translation Efficiency and Overcomentioning

confidence: 99%

mRNA vaccine for cancer immunotherapy

2021

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AbstractmRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

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Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

et al. 2021

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Chemical ligation reaction of DNA is useful for the construction of long functional DNA using oligonucleotide fragments that are prepared by solid phase chemical synthesis. However, the unnatural linkage structure formed by the ligation reaction generally impairs the biological function of the resulting ligated DNA. We achieved the complete chemical synthesis of 78 and 258 bp synthetic DNAs via multiple chemical ligation reactions with phosphorothioate and haloacyl‐modified DNA fragments. The latter synthetic DNA, coding shRNA for luciferase genes with a designed truncated SV promoter sequence, successfully induced the expected gene silencing effect in HeLa cells.

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Squaramides and Ureas: A Flexible Approach to Polymerase‐Compatible Nucleic Acid Assembly

Cited by 4 publications

References 42 publications

A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility

A New 1,5-Disubstituted Triazole DNA Backbone Mimic with Enhanced Polymerase Compatibility

mRNA vaccine for cancer immunotherapy

Completely Chemically Synthesized Long DNA Can be Transcribed in Human Cells

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