Synthesis of Readily Accessible Triazole-Linked Dimer Deoxynucleoside Phosphoramidite for Solid-Phase Oligonucleotide Synthesis

Chandrasekhar, Srivari; Srihari, P.; Nagesh, Chidalla; Nayani, Kiranmai; Nagesh, Narayana; Idris, Mohammed M.

doi:10.1055/s-0030-1258243

Cited by 18 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Replacement of the oligonucleotide phosphodiester linkage with triazole linkages has shown great promise [57][58][59][60]. These triazole analogs can be obtained through automated phosphoramidite synthesis with modified dinucleoside blocks [61] or the click reaction between azide-and alkyne-bearing nucleosides [62,63]. Figure 9 shows three types of promising triazole internucleotide modifications [64].…”

Section: Replaced By Triazolementioning

confidence: 99%

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Yao

Wang

et al. 2017

IJMS

246

181

View full text Add to dashboard Cite

Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.

show abstract

Section: Replaced By Triazolementioning

confidence: 99%

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Yao

Wang

et al. 2017

IJMS

246

181

View full text Add to dashboard Cite

show abstract

“…This modification is usually achieved using a click reaction between azide-and alkyne-bearing nucleosides ( Figure 13) [112,113] or through automated phosphoramidite synthesis with modified dinucleoside blocks ( Figure 14) [114]. The triazole unit can link nucleotides directly or with methylene or single ether bond linkage.…”

Section: Triazole Modificationmentioning

confidence: 99%

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

et al. 2019

View full text Add to dashboard Cite

Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems. Molecules 2020, 25, 3 2 of 51 molecules [2]. Nowadays, the aptamer field covers various biomedical applications, including [3], therapeutic [4-6], aptasensors [7], biosensors [8,9], diagnostic [10,11], and imaging systems [12].Aptamers need to be stabilized for in vivo use against nuclease degradation, and their small size makes them susceptible to renal filtration. Aptamers' stabilization can be attained by chemically modifying them using different approaches. Moreover, introducing chemical modifications into nucleic acid libraries increases the interaction capabilities of aptamers and thereby their target spectrum [12]. Modified aptamers may show improved chemical diversity relative to aptamers composed entirely of natural DNA or RNA nucleotides and expand their applications in diagnostics, therapeutics, and nanotechnology [1].Chemical modifications of aptamer oligonucleotides are needed mainly to enhance their resistance to nuclease degradation and lowering their renal filtration. Additionally, chemical modifications, in some cases, may increase the aptamer-binding affinity [13]. Many approaches have been introduced to promote the stability of aptamers without altering their binding affinity and specificity against their targets. These approaches include chemical modification of the phosphate...

show abstract

“…Examples of DNA‐based triazole‐phosphoramidites include the following studies: Chandrasekhar et al. () and Varizhuk et al. ().…”

Section: Commentarymentioning

confidence: 99%

“…Fujino and coworkers have designed oligomers of deoxyribonucleotides through iterative cycloadditions. Examples of DNA-based triazolephosphoramidites include the following studies: Chandrasekhar et al (2010) and Varizhuk et al (2012). Examples of triazole-backbone units within RNA include the following studies: El-Sagheer and Brown (2010) and Fujino et al (2012).…”

Section: Background Informationmentioning

confidence: 99%

Synthesis of Triazole‐Nucleoside Phosphoramidites and Their Use in Solid‐Phase Oligonucleotide Synthesis

Peel

Efthymiou

Desaulniers

2013

CP Nucleic Acid Chemistry

View full text Add to dashboard Cite

Triazole-backbone oligonucleotides are macromolecules that have one or more triazole units that are acting as a backbone mimic. Triazoles within the backbone have been used within oligonucleotides for a variety of applications. This unit describes the preparation and synthesis of two triazole-nucleoside phosphoramidites [uracil-triazole-uracil (UtU) and cytosine-triazole-uracil (CtU)] based on a PNA-like scaffold, and their incorporation within oligonucleotides.

show abstract

Synthesis of Readily Accessible Triazole-Linked Dimer Deoxynucleoside Phosphoramidite for Solid-Phase Oligonucleotide Synthesis

Abstract: A concise preparation of triazole-linked deoxynucleoside phosphoramidite for its direct use in solid-phase oligonucleotide synthesis is reported. This dimer has successfully been utilized in solid-phase synthesis to make the 10-and 12-mer oligomers.

Cited by 18 publications

References 5 publications

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

Synthesis of Triazole‐Nucleoside Phosphoramidites and Their Use in Solid‐Phase Oligonucleotide Synthesis

Contact Info

Product

Resources

About