Ole Buchardt

Peptide nucleic acids

Peptide nucleic acids (PNAs) are attractive, as compared to other classes of oligonucleotides that have been developed to date, in that they are relatively easy to synthesize and modify, hybridize to DNA and RNA with high affi nity and sequence selectivity, and are resistant to enzymatic degradation by proteases and nucleases; however, the downside is that they are only moderately soluble in aqueous solution. Herein we describe the protocols for synthesizing the second-generation γPNAs, both the monomers and oligomers, containing MiniPEG side chain with considerable improvements in water solubility, biocompatibility, and hybridization properties.

Peptide nucleic acids and their potential applications in biotechnology

Peptide nucleic acids (PNAs) are novel DNA mimics in which the sugar-phosphate backbone has been replaced with a backbone based on amino acids. PNAs exhibit sequence-specific binding to DNA and RNA with higher affinities and specificities than unmodified DNA. They are resistant to nuclease and protease attack in serum and cellular extracts and, thus, appear very promising as diagnostic and biomolecular probes, and possibly as antisense and antigene drugs.

Peptide nucleic acid (PNA) with a chiral backbone based on alanine

Abstract A synthesis of N -(2-Boc-aminoethyl)- N -(thymin-1-ylacetyl)alanine ( 5 ) is presented. It is demonstrated that chiral integrity can be preserved. PNA (Peptide Nucleic Acid) containing the D-form of 5 hybridizes to complementary DNA with higher affinity than PNA containing the L-form of 5 .

ARYL AZIDES AS PHOTOAFFINITY LABELS. A PHOTOCHEMICAL STUDY OF SOME 4-SUBSTITUTED ARYL AZIDES

Abstract— The photochemistry of a series of aryl azides used in, or closely related to some of those used in photoaffinity labeling studies, has been investigated by flash photolysis, continuous irradiation and low‐temperature irradiation with IR and UV spectroscopic analysis. Results indicate that labeling preferentially takes place via singlet species. The reactive intermediates appear to be cycloazaheptatetraenes and/or the corresponding benzazirines. The reactive intermediates have τ½ of the order of milliseconds or shorter and oxygen may act as a quencher, thereby interfering with the affinity labeling.

A flexible and positively charged PNA analogue with an ethylene-linker to the nucleobase: Synthesis and hybridization properties

Abstract The positively charged and relatively flexible PNA unit ethT (Fig. 1) has an ethylene linker between backbone and nucleobase rather than the methylene carbonyl linker normally present in PNA. The synthesis of the corresponding modified monomer, its incorporation into PNA oligomers, and their hybridization properties to DNA are described.

Modification of the binding affinity of peptide nucleic acids (PNA). PNA with extended backbones consisting of 2-aminoethyl-β-alanine or 3-aminopropylglycine units

The binding affinity between peptide nucleic acids (PNA) and DNA is reduced by incorporation of PNA units with extended backbones.

Peptide nucleic acids containing adenine or guanine recognize thymine and cytosine in complementary DNA sequences

Peptide nucleic acid (PNA) monomer building blocks for the introduction of G and A are prepared and used to synthesise H-T4XT5-Lys-NH2(X = G or A), which are shown by Tm measurements to recognize their complementary DNA sequences in both the parallel (N-terminal PNA/5′-DNA) and the anti-parallel mode; the stoichiometry in each case is (PNA)2/DNA.

The synthesis, co-oligomerization and hybridization of a thymine-thymine heterodimer containing PNA

Abstract A peptide nucleic acid (PNA) decamer in which one of the amide bonds between two units is reversed was prepared and its binding affinity to complementary DNA is shown to be preserved.

A PNA-DNA LINKER SYNTHESIS OF N-((4,4'-DIMETHOXYTRITYLOXY)ETHYL)-N-(THYMIN-1-YLACETYL)GLYCINE

Abstract N -(2-benzyloxyethyl)- N -(thymin-1-ylacetyl)glycine was synthesised and used as a linker for coupling DNA and PNA together. Three different 10-mers composed of 6 DNA units and 4 PNA thymine units were made. The PNA-DNA chimera hybridise to complementary DNA or PNA oligomers, and both the PNA and the DNA part of the chimera are involved in the binding.

PNA-peptide chimerae

Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.