Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• instead of RNA and promotes a C2'-endo puckering of the sugar [147]. As a result, it has been shown to be better (fivefold) than other modified LNA analogues at knocking down target genes in vitro [145]. Also, these isomers have recently been shown to be useful in stabilizing streptavidin-binding aptamers

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• LNPs that can cross the BBB, we developed and assessed two approaches. The first was centered on the BBB-penetrating trans-activator of transcription (Tat) peptide or the peptide T7, and the other on RNA aptamers targeted to glycoprotein gp160 from human immunodeficiency virus (HIV) or C-C chemokine

• no need for additional reactions after cleavage [27][28][29]. One approach to generate LNP formulations with higher specificity for antigen-expressing cells is to use RNA aptamers. RNA aptamers are short oligonucleotides that are evolved using a process called systematic evolution of ligands by

• RNA aptamers as a mean to increase the specificity of LNPs for HIV-1-infected and/or target cells [31]. RNA aptamers are ideal candidates due to the lower immunogenicity profile than the DNA counterparts [30][32][33]. RNA aptamers are also highly amenable to form complex and dynamic secondary

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• function opens new possibilities for applications of oligonucleotides. Keywords: aptamer; ATP; bioinorganic chemistry; DNA; imidazole; metal-mediated base pairs; Introduction Aptamers are oligonucleotides capable of recognizing and binding to specific molecules up to the size of proteins [1]. While

• mostly unstructured in solution, aptamers typically fold into their three-dimensional structure upon binding the respective target molecule [2]. Aptamers are normally identified by the in vitro selection from combinatorial libraries of nucleic acids [3]. In the past decades, interest in aptamers has

• quadruplex, so that metal-mediated base pairs can be introduced. 3) It is a short oligonucleotide, so the modified aptamers can easily be synthesized using automated solid-phase synthesis. 4) The target molecule of this aptamer is a small molecule, facilitating the binding assays. 5) The aptamer also binds

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• involved in a number of essential biological functions including active transport and cell division [28][29]. For ATP detection, metal complexes using metal ions such as Zn(II), Cu(II) and lanthanide ions have been frequently employed [30][31][32][33][34][35]. A variety of other systems such as aptamers

A smart deoxyribozyme-based fluorescent sensor for in vitro detection of androgen receptor mRNA

• Ekaterina A. Bryushkova,
• Erik R. Gandalipov and
• Julia V. Nuzhina

Beilstein J. Org. Chem. 2020, 16, 1135–1141, doi:10.3762/bjoc.16.100

• two aptamers mentioned above was tested on full-length mRNA [26]. To investigate the ability of the proposed SDFS to selectively detect a full-length AR RNA we performed experiments on total RNA that was extracted from human dermal papilla cells (HDPC) obtained from the cell culture collection of the

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• to various stimuli and evaluate their applications, mainly focusing on the control of gene expression. The use of ON prodrugs as aptamers, decoys or immunostimulatory ONs in other ON-based therapeutic strategies is marginally mentioned. Two classes of stimuli can trigger inactive ON prodrugs in

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• these experiences as hindering our progress, they should be embraced and appreciated for their ability to lead to new discoveries. In this perspective, I will discuss the unexpected events that have shaped my career path and the early stages of my independent research program. Keywords: aptamers; DNA

• highlight some of these stories of unexpected results and what we learned from them. During my initial brainstorming of project ideas, I was very drawn to the idea of working with DNA split aptamers. These recognition elements are comprised of two DNA (or RNA) sequences that selectively assemble in the

• presence of a small-molecule or protein target [5][6]. Thus, they combine my two favorite themes, as they use molecular recognition to drive self-assembly. At the point that we began our research program, all of the reported work on split aptamers had focused on detecting non-covalent assembly for systems

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• co-workers elegantly extended the utility of SELEX [30] to generate aptamers functionalized with glycans through CuAAC [31][32]. Their approach, termed SELMA (selection with modified aptamers), is a multistep procedure that allows screening, selection and amplification of DNA glycoconjugates (Scheme

• strand displacement thus allowing the glycosylated strand to adopt a folded structure. Affinity selection and reiteration of the cycle enables the in vitro evolution of glycan-functionalized aptamers. This technology was used to screen ligands for 2G12, an antibody that neutralizes HIV by binding to the

• high mannose epitope of gp120. For this purpose, the aptamer library was functionalized with oligomannoses (Man4-azide or Man9-azide) leading to the selection of glycan-functionalized aptamers bearing 7–14 glycan units and with a KD below 220 nM. A mutagenesis study showed that the affinity was also

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional

• enabled by techniques such as solid phase synthesis, post synthetic modifications or enzymatic incorporation of modified analogues. Originating from research into aptamers as strong and selective binders [12][13][14], several research groups are investigating the creation and synthesis of new DNA or RNA

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With