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

• /bjoc.17.116 Abstract Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes

• for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications. Keywords: antisense; chemical modifications; diagnostics; peptide nucleic acid; PNA; Introduction Peptide nucleic acid (PNA) is a DNA mimic where the sugar–phosphate backbone of DNA is replaced with

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

• arguably the most radical alternative nucleic acid pairing system, peptide nucleic acid (PNA), the sugar-phosphate backbone is replaced by an amide-based, neutral and achiral scaffold that allows cross-pairing with both DNA and RNA as well as formation of double- and triple-stranded species [57]. Despite

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• first compounds here reported, may find applications in different fields such as chemical biology, nanotechnology and materials science. Keywords: azobenzene; hemithioindigo; peptide nucleic acid (PNA); photoswitch; visible-light irradiation; Introduction Light-driven control of oligonucleotide

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• illustrate a repetitive Ugi 4CR-deprotection-Ugi 4CR protocol to obtain peptide nucleic acid (PNA) oligomers (Scheme 13A) [49], peptidic tetrazoles and hydantoinimides (Scheme 13B) [50], respectively. Incidentally, the later processes take place in solid phase, which enhances their synthetic suitability. The

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

• linkages, with the nucleic acid mimic 'peptide nucleic acid' (PNA) [11][12][13] representing a striking example. Although the achiral PNA backbone is pronouncedly different from native nucleic acid structures, PNAs are capable of sequence-specific hybridization to native nucleic acids. However, their

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• been conjugated to a variety of molecules, including peptides [29], proteins [30], DNA [17], and DNA analogues such as peptide nucleic acid (PNA) [16][31]. TO-based chromophores assembled as a structural scaffold inside nucleic acids (TO-tethered nucleic acids) have attracted considerable attention [32

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• analogue with a peptide backbone carrying nucleobases on its amino acid side chains [42] while Bradley et al. used the backbone of a peptide nucleic acid (PNA) with abasic sites which gives a reactive secondary amine for reversible attachment of aldehyde modified nucleobases [43]. Moreover, the DNA

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

• glycosylated hybrids As an alternative to DNA, peptide nucleic acid (PNA) [34] has also been used to tag glycans and to program their assembly based on the rules of hybridization. From an assembly standpoint, stable PNA–DNA duplexes can be achieved with shorter sequences than the corresponding DNA homoduplex

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

• manipulate the charge pattern in the backbone and to enhance nuclease stability. The electroneutral nucleic acid mimic 'peptide nucleic acid' (PNA) [10][11][12] is capable of sequence-specific binding to nucleic acids, but it was found to display limited water solubility and a peptide-like folding behaviour

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• , pyrrolidinyl peptide nucleic acid (acpcPNA) was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV–vis and fluorescence spectroscopy in the absence and in the presence of DNA

• – has also been incorporated into DNA as a base replacement, again without showing significant structure-induced fluorescence change [22]. Peptide nucleic acid or PNA is an electrostatically neutral analogue of DNA which can form very stable duplexes with DNA and RNA in a highly sequence specific

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• , for example, used in a conformational analysis of the prolyl ring in aminoethylprolyl peptide nucleic acid monomers [13], or in a conformational analysis of 2’-fluoro-4’-thioarabinothymidine [14]. The performance of the Matlab Pseudorotation GUI program was tested on two 4’-thio-2’deoxynucleoside

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• recognition; triplex stabilization; Introduction Peptide nucleic acid (PNA) probes are very selective in the recognition of DNA and have been used in a large variety of diagnostic methods, easily allowing the detection of point mutations at very low concentrations [1][2][3]. Poly-pyrimidine PNA can form very

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• previously used in the synthesis of PMO in the 2→4 direction [23]. This corresponds to the 5’→3’ direction of native oligonucleotides. In our case, the MorGly oligomers were synthesized in the opposite direction (4→2) [20] similar to the standard direction (3’→5’) of native ODN and peptide nucleic acid (PNA