1,721,012 research outputs found
Effect of chirality in gamma-PNA: PNA interaction, another piece in the picture
No full textModification of the PNA backbone can be used to broaden their utility by introducing new functional groups. In particular, gamma-modified PNA have been found to be quite effective in a number of applications, and exhibit particularly high DNA binding affinity. The introduction of one side chain imply that the achiral backbone of PNA becomes chiral, and binding properties depend on the stereochemistry. A new paper on gamma-modified PNA by Ly and co-workers complete the existing knowledge by displaying that in binding to complementary PNA stereochemical orthogonality can be demonstrated. This opens the way to the exploitation of stereochemical features in diagnostic assays and in nanofabrication
Proximity-induced ligation and one-pot macrocyclization of 1,4-diketone-tagged peptides derived from 2,5-disubstituted furans upon release from the solid support
No full text1,4-Dione-containing peptides are generated during the cleavage of 2,5-disubstituted furan-containing systems. The generated electrophilic systems then react with a-effect nucleophiles, following a Paal-Knorr-like mechanism, for the generation of macrocyclic peptides, occurring after simple resuspension of the crude peptide in water. Conveniently, the in situ generation of the electrophile from a stable furan ring avoids the complications associated with the synthesis of carbonyl-containing peptides. Detailed investigation of the reaction characteristics was first performed on supramolecular coiled-coil systems
DNA-templated release of functional molecules with an azide-reduction-triggered immolative linker
No full textNucleic acid templated reactions have attracted significant attention for nucleic acid sensing. Herein we report a general design which extends the potential of nucleic acid templated reactions to unleash the function of a broad diversity of small molecules such as a transcription factor agonist, a cytotoxic or a fluorophore
Furan-PNA : a mildly inducible irreversible interstrand crosslinking system targeting single and double stranded DNA
Full text linkWe here report on the design and synthesis of tailor-made furan-modified peptide nucleic acid (PNA) probes for covalent targeting of single stranded DNA through a crosslinking strategy. After introducing furan-containing building blocks into a PNA sequence, hybridization and furan-oxidation based crosslinking to DNA is investigated. The structure of the crosslinked products is characterized and preliminary investigations concerning the application of these systems to double stranded DNA are shown
A Bifunctional Monomer for On-Resin Synthesis of Polyfunctional PNAs and Tailored Induced-Fit Switching Probes
Full text linkA synthetic
strategy for the production of polyfunctional PNAs
bearing substituent groups both on the nucleobase and on the backbone
C5 carbon of the same monomer is described; this is based on the use
of a tris-orthogonally protected monomer and subsequent solid-phase
selective functionalization. This strategy can be used for synthesizing
PNAs that are not readily accessible by use of preformed modified
monomers. As an example, a PNA-based probe that undergoes a switch
in its fluorescence emission upon hybridization with a target oligonucleotide,
induced by tailor-made movement of two pyrene substituent groups,
was synthesized
Furan-modified PNA probes for covalent targeting and ligation of nucleic acids
No full textWhile natural oligonucleotides (ONs) are increasingly used as therapeutic and diagnostic tools, they still face certain challenges such as low resistance to enzymatic degradation, potential immunogenicity, and delivery issues, which can limit their applications. Peptide Nucleic Acids (PNAs) are promising alternatives due to their high affinity for DNA and RNA, the high resistance to enzymatic degradation, and the easy introduction of a wide range of potential modifications. Chemical modifications that enable the covalent targeting of specific DNA and RNA strands offer additional advantages, including enhanced potency. The current study focuses on the utilization of furan-PNAs as pro-reactive probe systems and their applications to DNA and RNA targeting. Specifically, in this methodological paper, we provide practical insights into the design, synthesis, and application of furan-containing PNA probes for achieving efficient PNA-DNA and PNA-RNA interstrand crosslinking (ICL), as well as ON-templated PNA-PNA ligation systems. Furthermore, we discuss the applications of these probes in targeting DNA secondary structures, such as G-quadruplexes and i-motifs, target pull-down assays, and on-surface detection
Synthesis and Improved Cross-Linking Properties of C5-Modified Furan Bearing PNAs
No full textOver the past decades, peptide nucleic acid/DNA (PNA:DNA) duplex stability has been improved via backbone modification, often achieved via introducing an amino acid side chain at the α- or γ-position in the PNA sequence. It was previously shown that interstrand cross-linking can further enhance the binding event. In this work, we combined both strategies to fine-tune PNA crosslinking towards single stranded DNA sequences using a furan oxidation-based crosslinking method; for this purpose, γ-l-lysine and γ-l-arginine furan-PNA monomers were synthesized and incorporated in PNA sequences via solid phase synthesis. It was shown that the l-lysine γ-modification had a beneficial effect on crosslink efficiency due to pre-organization of the PNA helix and a favorable electrostatic interaction between the positively-charged lysine and the negatively-charged DNA backbone. Moreover, the crosslink yield could be optimized by carefully choosing the type of furan PNA monomer. This work is the first to describe a selective and biocompatible furan crosslinking strategy for crosslinking of γ-modified PNA sequences towards single-stranded DNA
Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA2DNA triplexes
No full textPyrene derivatives can be incorporated into nucleic acid analogs in order to obtain switchable probes or supramolecular architectures. In this paper, peptide nucleic acids (PNAs) containing 1 to 3 1-pyreneacetic acid units (PNA1–6) with a sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex formation, with stability depending on the number and positioning of the pyrene units along the chain. An increase in triplex stability and a very high mismatch-selectivity, derived from combined stacking and base-pairing interactions, were found for PNA2, bearing two distant pyrene units
Building on the peptide nucleic acid (PNA) scaffold: a biomolecular engineering approach
No full textPeptide nucleic acids (PNAs) are polyamide analogues of nucleic acids, very effective in terms of affinity and selectivity in DNA/RNA recognition. As other supramolecular entities, the PNA structure has been an interesting scaffold for the development of new molecules, aimed to DNA and RNA recognition, with improved or completely new properties. This review describes recent work, with the aim of describing how the design of these molecules has evolved in recent years, using increasingly effective tools, from simple crystal structure analysis to molecular dynamics and metadynamics. Modified PNA with additional modules appended, either on the backbone or on the nucleobase, are described. Polyfunctional molecules with both backbone and nucleobase modification are then considered. Finally, recent examples of architectures obtained by conjugation of PNAs to inorganic nanostructures as cargo systems for diagnostics and nano-biotechnology are presented
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