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

• to the lack of electrostatic repulsion [1][2][3]. As will be reviewed below, because of its robust metabolic stability and high affinity and sequence specificity, PNA has become a vital component of many research assays and diagnostics [4]. Nevertheless, PNA has not been without shortcomings and

• cationic RNA binding compounds, perhaps, because the protonation event is coupled with the Hoogsteen hydrogen bond formation. As a result, the partially protonated M strengthens the triple helix without compromising the sequence specificity of recognition [28][30][31]. As discussed above, guanidine groups

• bonding options on the purine base as well. An extended nucleobase S (Figure 7) originally developed for triplex-forming oligonucleotides [114][115], was introduced in PNAs targeting U interruptions in polypurine tracts of dsRNA triplexes [111]. However, in PNA, S showed limited sequence specificity

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

• affinity with complementary RNA [35], and a destabilising effect on the thermal stability of G-quadruplexes [36] hinders its application. In contrast, a phosphate methylated linkage (POMe,) marginally destabilised complementary DNA but improved sequence specificity [37]. Recently, we synthesised a G-rich

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• tethering of two antiparallel polyamide segments increases the sequence specificity and the affinity of the polyamides to their cognate dsDNA. Different linker strategies were used, with γ-aminobutyric acid (γ) being the most successful representative. The resulting hairpin polyamides bound with 100-fold

• experiments and indicate a higher sequence specificity, e.g., of Z-P3. The highest binding affinity (lowest KD) was obtained for Z-P1, with a slight preference for the target DNA sequence compared to the single mismatch sequence. Binding affinity as well as duplex stabilization was lowest for Z-P2 for both

• did not induce ICD assigned to the polyamide chromophores, possibly because of the formation of small soluble aggregates. Z-P3, with a higher number of heterocyclic units, displayed some sequence specificity, albeit not in a range that was reported for other nonphotoswitchable polyamides. The (Z

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• as inhibitors of Werner and Bloom syndrome helicases and dual topoisomerase I/II inhibitors [37][38]. In order to improve DNA binding affinity and sequence specificity with reduced side effects, a series of synthetic hybrid molecules derived from distamycin and netropsin was synthesized and their

• affinity, sequence specificity, more cytotoxicity and minimizing the unwanted physiological side effects [43]. It has been observed that drugs with high degree of sequence specific binding affinity and selective alkylation of DNA could inhibit the binding of the regulatory proteins to DNA. Several

• structural analogs of distamycin, netropsin and thiazotropsins were developed to test their DNA binding affinity, sequence specificity and cytotoxicity, thereby eventually developing a general approach for the regulation of gene expression by DNA binding small molecules. However, all these analogs do not

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

• –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

• be efficiently delivered to the nucleus and bind to dsDNA with high affinity and sequence-specificity. MGBs recognize target sequences according to the well-established rules [6] with high affinity and without pH or ionic strength limitations. They penetrate into living cells and reach genomic DNA

• the most stable complexes are formed by antiparallel G-rich TINA-TFOs [17][18] (Figure 1). The conjugation of TINA-TFOs to MGBs should allow for recognition of longer sequences in dsDNA than for the parent components thus providing improved affinity and sequence specificity [11]. Using carbodiimide

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• addition of 10mer PNA 11, a large increase of diffusion times was observed that can only be explained by aggregation. Aggregation of PNA conjugates with complementary RNA but even with noncognate oligonucleotides [21] might cause a loss of sequence specificity. It was of critical importance, therefore, to

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• this system the n-butyl moiety provides insufficient discrimination towards α- and β-CD and no sequence specificity is observed. By the combination of three adamantane moieties sequence specificity can be generated. Exclusively with the complementary CD sequence double-stranded structures are formed

• , with non-complementary strands aggregates of higher stoichiometry are generated. Keywords: cooperativity; cyclodextrins; molecular recognition; multivalency; sequence specificity; Introduction Multivalency is the interaction of a receptor and a ligand with at least two recognition motifs on each

• overall binding model. Here all complexation steps are combined in one set of thermodynamic parameters. With this method similar binding constants and thermodynamic parameters are calculated for both interactions, so that no sequence-specificity in the complexation behavior of the divalent guest strand 8

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• ethylene-bridged base pair. Both linked A/T and G/C base pair analogs can conveniently be prepared which allows studying any base pair-opening enzyme regardless of its sequence specificity. The cross-link is stable in the absence of reducing agents but the linker can be quickly and tracelessly removed by

• . Both linked A/T and G/C base pair analogs can easily be prepared which allows studying any base flipping enzyme regardless of its sequence specificity. We demonstrated that cross-linked DNA is a useful tool to study base flipping enzymes and proved that the base flipping equilibrium lies mostly on the

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• expression in living cells has required the development of modified oligonucleotides as potential therapeutic agents. A key goal in the design of such agents include increasing binding affinity while maintaining sequence specificity, resistance to degradation by nucleases and improved membrane permeability