Improvements in automated PNA synthesis using Boc/Z monomers

Koch, Troels; Hansen, Henrik F.; Andersen, Peter Bøgh; Larsen, T; Batz, Hans‐Georg; Otteson, K M; Ørum, Henrik

doi:10.1111/j.1399-3011.1997.tb01124.x

Cited by 68 publications

(15 citation statements)

References 31 publications

(10 reference statements)

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“…; Koch et al . ). The carrier peptide, transportan (TP10), was synthesized on the 431A peptide synthesizer and purified before conjugation with PNA on a reverse‐phase HPLC C 18 column.…”

Section: Methodsmentioning

confidence: 97%

Cav1.2 and Cav1.3 L‐type calcium channels independently control short‐ and long‐term sensitization to pain

Radwani

López-González

Cattaert

et al. 2016

The Journal of Physiology

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Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short-term sensitization can be monitored through the study of wind-up. Wind-up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post-synaptic L-type calcium channels. In the dorsal horn of the spinal cord, two L-type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind-up, whereas Cav1.2 is not and that synaptically triggered wind-up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind-up was decreased. These results were confirmed with our model when adapting Cav1.3 conductance to the changes observed after SNL. Finally, our mathematical approach predicts that, although wind-up amplitude is decreased in SNL, plateau potentials are not altered, suggesting that plateau and wind-up are not fully equivalent. Wind-up and long-term hyperexcitability of DHNs are differentially controlled by Cav1.2 and Cav1.3, therefore confirming that short- and long-term sensitization are two different phenomena triggered by distinct mechanisms.

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“…; Koch et al . ). The carrier peptide, transportan (TP10), was synthesized on the 431A peptide synthesizer and purified before conjugation with PNA on a reverse‐phase HPLC C 18 column.…”

Section: Methodsmentioning

confidence: 97%

Cav1.2 and Cav1.3 L‐type calcium channels independently control short‐ and long‐term sensitization to pain

Radwani

López-González

Cattaert

et al. 2016

The Journal of Physiology

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“…Ethyl esters of phosphonic acid are highly stable under physiologic conditions and against esterases [39]. All PNAs were synthesized on a fully automated solid phase synthesizer (Multisynthec Syro) according to a protocol developed by Koch [40]. aegPNAs (Six3-aegPNA) were synthesized by Eurogentec.…”

Section: Methodsmentioning

confidence: 99%

Side chain modified peptide nucleic acids (PNA) for knock-down of six3in medaka embryos

et al. 2012

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BackgroundSynthetic antisense molecules have an enormous potential for therapeutic applications in humans. The major aim of such strategies is to specifically interfere with gene function, thus modulating cellular pathways according to the therapeutic demands. Among the molecules which can block mRNA function in a sequence specific manner are peptide nucleic acids (PNA). They are highly stable and efficiently and selectively interact with RNA. However, some properties of non-modified aminoethyl glycine PNAs (aegPNA) hamper their in vivo applications.ResultsWe generated new backbone modifications of PNAs, which exhibit more hydrophilic properties. When we examined the activity and specificity of these novel phosphonic ester PNAs (pePNA) molecules in medaka (Oryzias latipes) embryos, high solubility and selective binding to mRNA was observed. In particular, mixing of the novel components with aegPNA components resulted in mixed PNAs with superior properties. Injection of mixed PNAs directed against the medaka six3 gene, which is important for eye and brain development, resulted in specific six3 phenotypes.ConclusionsPNAs are well established as powerful antisense molecules. Modification of the backbone with phosphonic ester side chains further improves their properties and allows the efficient knock down of a single gene in fish embryos.

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“…All CMCOs were synthesized on a fully automated solidphase synthesizer (Multisynthec Syro) according to a protocol developed by Koch et al (25). Whereas phosphonic ester side chains are synthesized to every nucleoside on type A CMCOs (see Table 1, bold), type B CMCOs are a mix of modified (see Table 1, bold) and nonmodified (see Table 1, underlined) nucleosides.…”

Section: Cmcos Are Designed By Addition Of Phosphonic Ester Residuesmentioning

confidence: 99%

Inhibition of Human Immunodeficiency Virus Replication by Cell Membrane-Crossing Oligomers

Posch

Piper²,

Lindhorst³

et al. 2011

Mol Med

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Although rapidly becoming a valuable tool for gene silencing, regulation or editing in vitro, the direct transfer of small interfering ribonucleic acids (siRNAs) into cells is still an unsolved problem for in vivo applications. For the first time, we show that specific modifications of antisense oligomers allow autonomous passage into cell lines and primary cells without further adjuvant or coupling to a cell-penetrating peptide. For this reason, we termed the specifically modified oligonucleotides "cell membrane-crossing oligomers" (CMCOs). CMCOs targeted to various conserved regions of human immunodeficiency virus (HIV)-1 were tested and compared with nontargeting CMCOs. Analyses of uninfected and infected cells incubated with labeled CMCOs revealed that the compounds were enriched in infected cells and some of the tested CMCOs exhibited a potent antiviral effect. Finally, the CMCOs did not exert any cytotoxicity and did not inhibit proliferation of the cells. In vitro, our CMCOs are promising candidates as biologically active anti-HIV reagents for future in vivo applications.

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Improvements in automated PNA synthesis using Boc/Z monomers

Cited by 68 publications

References 31 publications

Cav1.2 and Cav1.3 L‐type calcium channels independently control short‐ and long‐term sensitization to pain

Cav1.2 and Cav1.3 L‐type calcium channels independently control short‐ and long‐term sensitization to pain

Side chain modified peptide nucleic acids (PNA) for knock-down of six3in medaka embryos

Inhibition of Human Immunodeficiency Virus Replication by Cell Membrane-Crossing Oligomers

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