‘Retro–inverso’ peptide nucleic acid (PNA) monomers of thymine (T*:
N-(amidomethyl)-
N-(
N
1-thyminylacetyl)-β-alanyl) (and adenine) have been prepared and introduced in PNA oligomers. A homo ...‘retro–inverso’ T*
8 PNA was found not to hybridize to a complementary DNA or RNA oligonucleotide, whereas introduction of one retro–inverso thymine unit into the middle of a normal PNA 15-mer resulted in a ca. 8
°C destabilization of the complex of this oligomer with a complementary DNA or RNA oligomer. In an effort to compensate for the structural nucleobase ‘phase-shift’ caused by the T* monomer by also introducing a β-alanine monomer it is concluded that the effect of the T* backbone is −7
°C when hybridizing to DNA and −4.5
°C when hybridizing to RNA. Nonetheless, the T* unit shows good sequence discrimination comparable to that of normal PNA. Molecular dynamics simulations indicate an unfavourable conformation of the backbone amide carbonyl group resulting in reduced interaction with the aqueous medium and an ‘electrostatic clash’ with the carbonyl of the nucleobase linker. These results show that a simple inversion of an amide bond in the PNA backbone has a dramatic, and hardly predictable, effect on the DNA mimicking properties of the oligomer.
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Abbreviations used: T:
N-(amidoethyl)-
N-(
N
1-thyminylacetyl) glycinyl (n=2, m=1) β-ala-T:
N-(amidoethyl)-
N-(
N
1-thyminylacetyl)-β-alanyl (n=2, m=2), T*:
N-(amidomethyl)-
N-(
N
1-thyminylacetyl)-β-alanyl (n=1, m=2)
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Novel monomeric building blocks
4a and
4b of peptide nucleic acids with an
N-(aminomethyl) β-alanine backbone (‘retro-inverso’ PNA) are conveniently synthesized
via Hofmann rearrangement. In the ...major rotamer the side chain carbonyl points toward the C terminus.
The synthesis of a new DNA analogue based on ornithine is described. Only the thymine analogue was synthesised. A 10 mer entirely made up of the thymine monomer forms a triple helix with poly RNA A. ...The T
m of the triplex was 21°C.
The synthesis of a new DNA analogue based on ornithine is described. Only the thymine analogue was synthesised. A 10 mer entirely made up of the thymine monomer forms a triple helix with poly RNA A. The T
m of the triplex was 21°C.
Radioactive labelling of PNA has been performed by linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.
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