Peptide nucleic acids (PNA) derived from N-(N-methylaminoethyl)glycine. Synthesis, hybridization and structural properties

Backbone N-methylated peptide nucleic acids (PNAs) containing the four nucleobases adenine, cytosine, guanine and thymine were synthesized via solid phase peptide oligomerization. The oligomers bind to their complementary target with a thermal stability that is 1.5-4.5 degrees C lower per "N-methyl nucleobase unit" [dependent on the number and position(s) of the N-methyl] than that of unmodified PNA. However, even fully N-methyl modified PNAs bind as efficiently to DNA or RNA targets as DNA itself. Furthermore, the hybridization efficiency per N-methyl unit in a PNA decreased with increasing N-methyl content, and the effect was more pronounced when the N-methyl backbone units are present in the Hoogsteen versus the Watson-Crick strand in (PNA)(2)-DNA triplexes. Interestingly, CD spectral analyses indicate that 30% (3 out of ten) substitution with N-methyl nucleobases did not alter the structure of PNA-DNA (or RNA) duplexes or (PNA)(2)-DNA triplexes, and likewise CD spectroscopy and X-ray crystallography showed no major structural differences between N-methylated (30%) and unmodified PNA-PNA duplexes. However, PNA-DNA duplexes as well as triplexes adopted a different conformation when formed with all-Ai-methyl PNAs.

Rasmussen, H. (author)
Schmidt, G. (author)
Jensen, D.K. (author)
Sandholm Kastrup, J. (author)
Wittung Stafshede, Pernilla,1968Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)perwit (author)
Nordén, Bengt,1945Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)norden (author)
Buchardt, O. (author)
Nielsen, P.E. (author)
Chalmers tekniska högskola (creator_code:org_t)

By the author/editor: Haaima, G.; Rasmussen, H.; Schmidt, G.; Jensen, D.K.; Sandholm Kastrup ...; Wittung Stafshed ...; show more...; Nordén, Bengt, 1 ...; Buchardt, O.; Nielsen, P.E.; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Physical Chemist ...

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