Optimization of the binding properties of PNA-(5')-DNA chimerae.
The synthesis and evaluation of PNA-(5')-DNA chimerae containing either a 5'-amide (i.e. 1a), a 5'-phosphodiester (i.e. 1b) or 5'-phosphonate linkages (i.e. 1c,d) at the junction site are described. The 5'-linkages could be installed using either 5'-amino-5'-deoxythymidine phosphoramidite 2, O-[2-(2-aminoethyl)-(thymin-1-ylacetyl)amino]ethyl phosphoramidite 3, N-(2-aminoethyl)-N-(thymin-1-ylacetyl)aminomethyl phosphonate 4 or N-(2-aminoethyl)-N-(allyloxycarbonyl)aminomethyl phosphonate 5 as building blocks, respectively. It is shown that PNA-(5')-DNA of type 1a-c have a higher binding affinity with complementary RNA than native DNA, and that the antisense activity is mainly due to RNase H.
van der Laan
A C
AC
Leiden Institute of Chemistry, Gorlaeus Laboratories, The Netherlands.
Havenaar
P
P
Oosting
R S
RS
Kuyl-Yeheskiely
E
E
Uhlmann
E
E
van Boom
J H
JH
D002678:Chimera; D004247:DNA / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D008956:Models, Chemical; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism*; D009693:Nucleic Acid Hybridization / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis; D020135:Peptide Nucleic Acids / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D016914:Ribonuclease H / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018076:DNA, Complementary; D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA; D016914:Ribonuclease H