Generation of Aptamers with an Expanded Chemical Repertoire

Diafa, Stella; Hollenstein, Marcel

doi:10.3390/molecules200916643

Cited by 99 publications

(83 citation statements)

References 171 publications

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“…A large repertoire of chemically-modified nucleotide analogs with remarkable biophysical properties have been developed in recent years and a few papers have reviewed the use of these chemically-modified nucleotides in the generation of aptamers and nucleic acids with enzymatic activity including DNAzymes and ribozymes 14-18 . But, their applicability in de novo evolution of aptamers via SELEX methodologies are rather impeded by poor or lack of enzymatic recognition capabilities.…”

Section: Evolution Of Chemically-modified Aptamersmentioning

confidence: 99%

In vitroevolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

et al. 2016

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Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries.

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Section: Evolution Of Chemically-modified Aptamersmentioning

confidence: 99%

In vitroevolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

et al. 2016

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“…Modifications at both sugar positions are best tolerated with pyrimidines, and as a compromise between stability and the efficiency of synthesis, mixed libraries of modified pyrimidines and natural purines are commonly employed. 2’-F substituents have been used the most (reviewed in [1]), and 2’-F-pyrimidine-modified libraries have recently been subjected to in vivo selection for stable aptamers targeting tumor cells in living animals [2] or that penetrate the blood-brain barrier [3], and the Soh group has recently demonstrated the utility of including selection pressure for specificity to identify 2’-F-pyrimidine-modified RNA aptamers that recognize different subunits of integrin αVβ3 [4]. Optimized conditions and the use of the Y639F/H784A double mutant of T7 RNAP has also enabled the transcription of oligonucleotides with increased levels of 2’-OMe substitutions, which have been used for the identification of stabilized aptamers against vascular endothelial growth factor (VEGF) [5] and staphylococcal protein A [6].…”

Section: Selex With Modified Rna and Dnamentioning

confidence: 99%

The expanding world of DNA and RNA

Chen

Hongdilokkul

Liu

et al. 2016

Current Opinion in Chemical Biology

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DNA and RNA are remarkable because they can both encode information and possess desired properties, including the ability to bind specific targets or catalyze specific reactions. Nucleotide modifications that do not interfere with enzymatic synthesis are now being used to bestow DNA or RNA with properties that further increase their utility, including phosphate and sugar modifications that increase nuclease resistance, nucleobase modifications that increase the range of activities possible, and even whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs that increase the information content. These modifications are increasingly being applied both in vitro and in vivo, including in efforts to create semi-synthetic organisms with altered or expanded genetic alphabets.

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“…The ability of nucleic acids to bind a wide variety of targets ranging from metal ions to cells is remarkable in view of their limited chemical diversity. However, increasing the chemical diversity of nucleic acid polymers in order to expand their functional properties has been a longstanding challenge . The conventional strategy for sequence‐defined incorporation of modifications throughout a nucleic acid polymer is to use polymerase‐catalyzed primer extensions with modified (deoxy)nucleotide triphosphates.…”

Section: Introductionmentioning

confidence: 99%

Influence of Linker Length on Ligase‐Catalyzed Oligonucleotide Polymerization

2019

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Ligase‐catalyzed oligonucleotide polymerization (LOOPER) that enables the sequence‐defined generation of DNA with up to 16 different modifications has recently been developed. This approach was used to develop new classes of diversely modified DNA aptamers for molecular recognition through in vitro evolution. The modifications in LOOPER are appended by use of a long hexane‐1,6‐diamine linker, which could negatively impact binding thermodynamics. Here we explore the incorporation of modifications with the aid of shorter linkers and the use of commercially available phosphoramidites and assess their efficiency and fidelity of incorporation. We observed that shorter linkers are less tolerated during LOOPER, with very short linkers providing high levels of error and sequence bias. An ethane‐1,2‐diamine linker was found to be optimal in terms of yield, efficiency, and bias; however, codon adjustment was necessary. This shorter‐linker anticodon set for LOOPER should prove valuable in exploring the impact of diverse chemical modifications on the molecular function of DNA.

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Generation of Aptamers with an Expanded Chemical Repertoire

Cited by 99 publications

References 171 publications

In vitroevolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

In vitroevolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

The expanding world of DNA and RNA

Influence of Linker Length on Ligase‐Catalyzed Oligonucleotide Polymerization

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