Fmoc mediated synthesis of Peptide Nucleic Acids

Thomson, Stephen A.; Josey, John A.; Cadilla, Rodolfo; Gaul, Micheal D.; Hassman, C. Fred; Luzzio, Michael J.; Pipe, Adrian; Reed, Kathryn L.; Ricca, Daniel J.; Wiethe, Robert W.; Noble, Stewart A.

doi:10.1016/0040-4020(95)00286-h

Cited by 241 publications

(230 citation statements)

References 20 publications

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“…the first step by using the appropriate acid chloride or Mmt chloride in pyridine. The resulting benzyloxycarbonyl, [9,20,27] 4-tert-butylbenzoyl, anisoyl, [22,26] and Mmt derivatives [25] are then N 1 -alkylated with methyl bromoacetate [25±27] or tert-butyl bromoacetate [20] . Finally, cleavage of the ester group under basic or acidic conditions gives the corresponding cytosyl acetic acid derivative.…”

Section: Pna Monomeric Building Blocks With An Aminoethylglycine Backmentioning

confidence: 99%

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

Uhlmann¹,

Peyman²,

Breipohl³

et al. 1998

Angewandte Chemie International Edition

397

217

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The astonishing discovery that peptide nucleic acids (PNAs, B=nucleobase), in spite of their drastic structural difference to natural DNA, are better nucleic acid mimetics than many other oligonucleotides has resulted in an explosion of research into this class of compounds. The synthesis, physical properties, and biological interactions of PNAs as well as their chimeras with DNA and RNA are summarized here.

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Section: Pna Monomeric Building Blocks With An Aminoethylglycine Backmentioning

confidence: 99%

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

Uhlmann¹,

Peyman²,

Breipohl³

et al. 1998

Angewandte Chemie International Edition

397

217

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“…Fmoc (Bz, benzyl)/(iBu, isobutyl)-protected PNA was used. To improve the coupling efficiency of the first PNA moiety, a double coupling cycle was employed (40). Upon completion of the last elongation cycle, the terminal Fmoc group was cleaved by piperidine treatment, and the primary amine was acetylated.…”

Section: Synthetic Oligonucleotides and Peptidementioning

confidence: 99%

Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Borgatti¹,

Lampronti²,

Romanelli³

et al. 2003

Journal of Biological Chemistry

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Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We determined whether double-stranded molecules based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and, therefore, could act as decoy reagents able to inhibit molecular interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theoretically alter the molecular structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDPbased decoy molecules are more resistant than DNA/ DNA hybrids to enzymatic degradation appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.In vitro transfection of cis elements that decoy against nuclear factors leads to alteration of gene expression and was recently proposed in molecular medicine as a novel tool for the possible therapy of several disorders (1-12). One of the most effective decoy approaches so far described involves nuclear proteins belonging to the NF-B 1 superfamily (7-9, 13-20).Decoy molecules against NF-B inhibit the expression of NF-B regulated genes (MHC complex genes, IL2 receptor ␣, Igk, IL6, ␦ opioid receptor, preprogalanin, adhesion molecule-1) (20). More recently, dumbell DNA decoy elements against NF-B were demonstrated to be active in inhibiting ex vivo transcription driven by the long terminal repeat (LTR) of human immunodeficiency type-1 virus (HIV-1) (19). In addition to proteins belonging to the NF-B superfamily, decoy molecules for other target transcription factors, such as HNF-1, RFX1, nuclear factor YB, E2F, cAMP-response element, and Sp1, were found to be effective (1-6, 10 -12, 21).As to the molecular targets for the decoy approach, proteins belonging to the Sp1 family are of great interest since these transcription factors are involved in the regulation of the expression of several genes relevant to human pathologies, including those encoding vascular endothelial growth factor, plasminogen-activator inhibitor type-1 (PAI-1), COL1A2, urokinase-type plasminogen activator (uPA), and uPA receptor (3,(21)(22)(23)(24)(25). Sp1 binding sites are also present in the HIV-1 LTR (26). Thus, the development of experimental approaches based on Sp1 decoys to modulate the transcription of Sp1-dependent genes appears to be of great interest (3).Rec...

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“…3 Concomitant with the high interest that PNA elicited, a variety of chemistries were developed for the synthesis of oligomers that spanned Boc, Fmoc and Mmt-based oligomerization strategies among others. 2,[4][5][6] Our own interest in developing PNA chemistry was driven by the need for orthogonal protecting groups for the synthesis of nucleobase modified PNAs. 7,8 PNA bearing modified nucleobases have been explored for endowing PNA oligomers with new biophysical properties, as a labeling strategy, or to incorporate expanded functionality such as fluorescence.…”

Section: Introductionmentioning

confidence: 99%