Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d

• class-I riboswitch [1]. This riboswitch acts as a ribozyme by using 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as methyl group donor; it catalyzes self-methylation of a specific cytidine in the aptamer binding pocket, yielding N3-methyl cytidine (m3C) under release of 7-aminomethyl-7-deazaguanine

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• entities in our ribozyme design projects [21][22]. Strikingly, the C8-position of a specific adenosine in the loop region of the flavine mononucleotide (FMN) aptamer is a highly favorable position for covalent attachment of FMN to study regulation of an FMN dependent hairpin aptazyme in response to RNA

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• investigations into low temperature ice eutectic phases as the incubators of early life [120] and separately, the effects of high hydrostatic pressures upon ribozyme activities [121][122], it is surprising how little consideration has been given to the role of nucleic acid mechanochemistry under prebiotic

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• ribozyme, the spliceosome and RNAse P) share a common mechanism that sets them apart from reactions catalyzed by small ribozymes or protein enzymes [42][105]. Perhaps most strikingly, the large ribozymes do not make use of the vicinal 2´-OH as a nucleophile but instead fold into an elaborate tertiary

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

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• association with the interface of chemical systems. For instance, the activity of an RNA polymerase ribozyme was improved when the various RNA compounds of the system (the ribozyme, the template/primer) were derivatized with amphiphilic moieties and co-associated within micelle structures [69]. Although no

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• the individual ribozymes. Moreover, cooperative systems are generally more stable towards parasites then autocatalytic self-replicators and are, in principle, able to gain in complexity [46][47]. In the study a ribozyme of around 200 nucleotides called Azoarcus was used. This ribozyme is made from

• Azoarcus ribozyme was fragmented in two different pieces in three different ways, creating three different pairs I1, I2 and I3 which are shown encircled in Figure 10b. Furthermore, the target and IGS sequences were altered such that autocatalytic self-replication is minimized. The sequence was, however

• , chosen such that the IGS of one pair is matched to the target sites of the next pair. In this way one ribozyme, say E1, can catalyze the formation of the next ribozyme, E2, from its non-covalently bound building blocks I2. This ribozyme can in turn catalyze the formation of E3 from its building block and

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• modern RNA research, in particular for atomic mutagenesis experiments to explore mechanistic aspects of ribozyme catalysis. Here, we report the 5-step synthesis of a c3A phosphoramidite from cost-affordable starting materials. The key reaction is a silyl-Hilbert–Johnson nucleosidation using unprotected 6

• building blocks for RNA solid-phase synthesis represents a severe bottleneck in modern RNA research, in particular for studies that aim at the mechanistic elucidation of site-specific backbone cleavage of recently discovered ribozyme classes, known as twister, twister sister, pistol, and hatchet RNA

• motives [1][2]. Selected adenines in their active sites have been discussed to participate in acid base catalysis, thereby contributing to accelerate the specific phosphodiester cleavage of these nucleolytic ribozymes. Concerning the twister ribozyme, structural analyses suggest that an adenine N3 atom

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

• is often a problem. Moreover achieving control in terms of number, positioning and exact location of the desired catalytic moieties is far from straightforward. In contrast to the existing variety of rather complicated and unpredictable RNA based ribozyme-like structures, oligonucleotide duplexes

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

• the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine

• derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated. Keywords: cytidine deaminase; modified nucleoside; nucleic acids; ribozyme; RNA world

• which no ribozyme analogue has yet been found. This applies for example to the transformation of cytidine to uridine, which is a well-known RNA editing event in modern cellular chemistry [9]. This process is catalyzed by cytidine deaminases (CDA, EC 3.5.4) belonging to a family of enzymes found in pro