Chemistry for the synthesis of nucleobase-modified peptide nucleic acid

Hudson, R. H. E.; Viirre, R. D.; Liu, Y. H.; Wojciechowski, F.; Dambenieks, A. K.

doi:10.1351/pac200476071591

Pure Appl. Chem., 2004, Vol. 76, No. 7-8, pp. 1591-1598

http://dx.doi.org/10.1351/pac200476071591

Chemistry for the synthesis of nucleobase-modified peptide nucleic acid

R. H. E. Hudson, R. D. Viirre, Y. H. Liu, F. Wojciechowski and A. K. Dambenieks

Department of Chemistry, The University of Western Ontario, London, Ontario N6A 5B7, Canada

Abstract: Peptide nucleic acid (PNA) presents a versatile scaffold for chemical modifications that may benefit its solubility and hybridization properties, conjugation chemistry, cell membrane permeability, and so forth. We have employed straightforward chemical methods for the synthesis of PNA monomers containing C5-or C6-modified pyrimidines.The C5-modified pyrimidines are based on 5-hydroxymethyl-uracil or cytosine, or are achieved by cross-coupling from the 5-iodonucleobase derivatives, while C6 modifications are accessed from 6-carboxyuracil (orotic acid). We have also developed an on-resin activation/conversion of uracil-containing PNA oligomers to N⁴-cytosine-containing derivatives.