Peptide nucleic acid conjugates and their antimicrobial applications—a mini-review

Tsylents, Uladzislava; Siekierska, Izabela; Trylska, Joanna

doi:10.1007/s00249-023-01673-w

Cited by 8 publications

(3 citation statements)

References 85 publications

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“…CLIP6-PNAs were shown to have superior cellular uptake in cancer cells (U87-GBM, glioblastoma multiform) [55]. The FIT-PNA and cpFIT-PNA sequence is a 17-mer PNA that was selected based on the accessibility of this probe to an unfolded region in FLJ22447 lncRNA, as predicted by the RNA-fold software (http://rna.tbi.univie.ac.at/cgi-bin/ RNAWebSuite/RNAfold.cgi (accessed on 4 March 2024).…”

Section: Fit-pna and Cpfit-pna Design And Synthesismentioning

confidence: 99%

“…A variety of cell-penetrating peptides (CPPs) have been used as a simple strategy for PNA delivery into cells including several recent in vitro [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] and in vivo [ 45 , 46 ] studies in eukaryotes as well as bacteria [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. As PNA is synthesized by standard peptide chemistry (Fmoc or t-BOC), the introduction of a CPP to either C or N termini is straightforward.…”

Section: Introductionmentioning

confidence: 99%

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Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)

Mannully,

Mahajna,

Nazzal

et al. 2024

Biomolecules

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Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.

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Section: Fit-pna and Cpfit-pna Design And Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)

Mannully,

Mahajna,

Nazzal

et al. 2024

Biomolecules

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“…Importantly, since PNA structure differs from both peptides and nucleic acids, it is not recognized by proteolytic and nucleolytic enzymes and is resistant to both ( Wojciechowska et al, 2020 ). These advantages highlight the PNA potential in gene targeting strategies, both in diagnosis and as antimicrobial agents [reviewed in Saarbach et al (2019) ; Wojciechowska et al (2020) ; Perera et al (2021) ; Tsylents et al (2023) ].…”

Section: Introductionmentioning

confidence: 99%

Iron uptake pathway of Escherichia coli as an entry route for peptide nucleic acids conjugated with a siderophore mimic

Tsylents,

Burmistrz,

Wojciechowska

et al. 2024

Front. Microbiol.

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Bacteria secrete various iron-chelators (siderophores), which scavenge Fe3+ from the environment, bind it with high affinity, and retrieve it inside the cell. After the Fe3+ uptake, bacteria extract the soluble iron(II) from the siderophore. Ferric siderophores are transported inside the cell via the TonB-dependent receptor system. Importantly, siderophore uptake paths have been also used by sideromycins, natural antibiotics. Our goal is to hijack the transport system for hydroxamate-type siderophores to deliver peptide nucleic acid oligomers into Escherichia coli cells. As siderophore mimics we designed and synthesized linear and cyclic Nδ-acetyl-Nδ-hydroxy-l-ornithine based peptides. Using circular dichroism spectroscopy, we found that iron(III) is coordinated by the linear trimer with hydroxamate groups but not by the cyclic peptide. The internal flexibility of the linear siderophore oxygen atoms and their interactions with Fe3+ were confirmed by all-atom molecular dynamics simulations. Using flow cytometry we found that the designed hydroxamate trimer transports PNA oligomers inside the E. coli cells. Growth recovery assays on various E. coli mutants suggest the pathway of this transport through the FhuE outer-membrane receptor, which is responsible for the uptake of the natural iron chelator, ferric-coprogen. This pathway also involves the FhuD periplasmic binding protein. Docking of the siderophores to the FhuE and FhuD receptor structures showed that binding of the hydroxamate trimer is energetically favorable corroborating the experimentally suggested uptake path. Therefore, this siderophore mimic, as well as its conjugate with PNA, is most probably internalized through the hydroxamate pathway.

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Special Issue: 18th Congress of the Polish Biophysical Society

Antosiewicz,

Gilbert,

Marszalek

2023

Eur Biophys J

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Peptide nucleic acid conjugates and their antimicrobial applications—a mini-review

Cited by 8 publications

References 85 publications

Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)

Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs)

Iron uptake pathway of Escherichia coli as an entry route for peptide nucleic acids conjugated with a siderophore mimic

Special Issue: 18th Congress of the Polish Biophysical Society

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