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.