Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• between 2–4 µg/mL [96]. In contrast to CypM, PznL has higher substrate specificity towards its peptide substrate. It required more than just an N-terminal arginine as a recognition element. PznL cannot accept peptide substrates that lack the polyheterocyclic peptide backbone modifications of plantazolicin

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physiochemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters

• , and examining the future design for ASOs. Keywords: antisense oligonucleotides; backbone modifications; cations; nucleobase modifications; sugar modifications; Introduction Antisense oligonucleotides (ASOs) are single-stranded (ss) oligomers composed of typically 10–25 nucleotides linked by

• phosphorus atom which, however, is beyond the scope of this summary. For a more in-depth account of cationic backbone modifications, we direct the reader to a recent review by Meng and Ducho [125]. Conclusion Cationic amine- and polyamine-conjugates/derivatives have the potential to improve the properties of

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• PNA was able to adopt to the conformations of DNA and RNA to some extent, the P-form was the naturally preferred helical conformation of PNA. PNA backbone modifications PNA design was originally assisted by simple computer modeling that replaced the phosphodiester backbone of DNA with pseudopeptide

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

• oligonucleotide-based therapeutics. In the present review, we will summarize the properties of selected backbone modifications (Figure 1) and discuss investigations regarding their structure and function and, if applicable, their importance for therapeutic applications. Review Internucleotide linkage

• improving metabolic stability, pairing properties (RNA affinity), protein binding and transport/cellular uptake are concerned, chemical modifications are a prerequisite for the discovery and development of oligonucleotide therapeutics [11][12][13][14][15]. Thus, the natural PS and 2'-OMe backbone

• modifications provide improved resistance to degradation by exo- and endonucleases and they both affect protein binding [16][17]. Eight of the now approved 13 oligonucleotide drugs feature the PS modification in the backbone and all four approved siRNA therapeutics: ONPATTRO® (patisiran, 2018), GIVLAARI

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• motifs, and nucleosyl amino acid (NAA)-derived modifications. The synthesis and properties of the corresponding oligonucleotide analogues are described. Keywords: backbone modifications; cations; DNA; oligonucleotides; zwitterions; Introduction Oligonucleotides have the unique ability to bind

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues. Keywords: backbone modifications; DNA; nucleic acids; oligonucleotides; stereoselective synthesis; zwitterions; Introduction

• backbone modifications for bioactive oligonucleotide analogues. These considerations have led to our recently reported design of a novel artificial internucleotide linkage named 'NAA-modification' (Figure 1) [38]. Ongoing synthetic and structure-activity relationship (SAR) studies on naturally occurring