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. la), 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)ami phosphonate 5 as building blocks, respectively. It is shown that PNA-(5')-DNA of type la-e have a higher binding affinity with complementary RNA than native DNA, and that the antisense activity is mainly due to RNase H. (C) 1998 Elsevier Science Ltd. All rights reserved.