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

• a neutral and achiral pseudopeptide backbone (Figure 1) [1]. PNA retains the natural DNA nucleobases that are connected to the amide-linked backbone through additional amide linkages. PNA was originally designed as a DNA mimic to improve the properties of triplex-forming oligonucleotides [1][2]. Two

• extensive studies reviewed below, PNA still needs innovative chemistry to break through in clinic and other in vivo applications. Review PNA binding modes to DNA and RNA PNA was originally designed with an expectation to improve the binding properties of negatively charged triplex-forming oligonucleotides

• PNA PNA nucleobases for Hoogsteen recognition of guanine: As discussed in the Introduction, PNA was originally designed with the idea that the neutral backbone would improve binding properties of triplex-forming oligonucleotides. However, electrostatic repulsion is not the only weakness of triple

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• , their potential in triplex forming oligonucleotides was also studied which concluded the formation of most stable triplexes with single incorporations of additional pyrimidine nucleobases connected via a propylene linker [71]. Hrdlicka and co-workers [24] synthesized 5-C-alkynyl-functionalized double

• participation of both nucleobases of the double-headed nucleotides in Watson–Crick base pairing. The same group also showed that a multiple incorporation of the double-headed nucleotide is also tolerated, but the double-headed nucleotides with the present design were not suitable as triplex-forming

• oligonucleotides [42]. Pedersen and Nielsen [35] synthesized a double-headed nucleoside with two different nucleobases, i.e., 2′-deoxy-2′-(thymine-1-yl)ethyluridine (11) (Scheme 3). The oxidative cleavage of the allyl group in TIPDS-protected 2-allyl-2-deoxyuridine 8 gave the TIPDS-protected hydroxynucleoside 9 as

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• recognise and cut DNA sequences, or CRISPR-CAS9 [8][9][10] and CAS9-constructs [11][12][13][14] which rely on large proteins to open the target duplex, triplex-forming oligonucleotides (TFOs) [15] can be designed to bind in a sequence-specific manner to double-stranded DNA (dsDNA) [16]. In forming the

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple

• –imidazole polyamides; sequence specificity: DNA; triplex-forming oligonucleotides; Introduction The recognition and detection of specific sequences in native genomic double-stranded DNA (dsDNA) is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1][2][3

• ]. Besides natural and engineered peptides or proteins, two synthetic substances are known to recognize and bind dsDNA in a sequence-specific manner: triplex-forming oligonucleotides (TFOs) [4][5] and pyrrole–imidazole polyamide minor groove binders (MGBs) [6][7]. TFOs recognize polypurine stretches in