New approach to solid phase synthesis of polyamide nucleic acids analogues (PNA) and PNA-DNA conjugates

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

“…The binding data for a (homopyrimidine PNA)/DNA chimera reported by Petersen et al [77] cannot be unambiguously interpreted, presumably for the same reasons. The T m data of Stetsenko et al, [21] on the other hand, show unambiguously that the DNA part of uracil-containing PNA/ DNA chimeras participates in binding to complementary DNA.…”

“…The Mmt-protected monomers described by us, [26] and others [21,24,33,34] (Figure 8) can be deprotected under much milder conditions (trichloroacetic acid), and thus do not have this disadvantage. In particular, the combination with base-labile protecting groups for the exocyclic amino functionalities of the nucleobases cytosine, adenine, and guanine allows deprotection conditions that are compatible with standard oligonucleotide synthesis.…”

“…The monomer synthesis is concluded by saponification of the methyl ester with sodium hydroxide in water/dioxane and subsequent purification by chromatography on silica gel with an eluent that contains triethylamine. Stetsenko et al [21] coupled thyminyl and uracil acetic acids, as their pentafluorophenyl active esters, to Mmt-Aeg-OEt. After saponification of the ethyl ester with sodium hydroxide the monomers are converted into their tetrabutylammonium salts.…”

“…The first synthesis of uracil-containing PNA/DNA chimeras was reported by Stetsenko et al [21] An Mmt protected uracil PNA monomer was used to assemble oligomers of type (II), again by using 5'-amino-5'-deoxythymidine as the DNA ± PNA linker. T m measurements of these chimeras indicated that the DNA part was involved in cooperative binding to the complementary nucleic acid.…”

“…A) Two routes for the synthesis of Mmt monomers. [21,26] B) Alternative synthesis of Mmt monomers: [36] a) ClCH 2 COCl, NEt 3 , THF; b) DMF, THF 4 ; c) thymine, K 2 CO 3 , DMF; d) NaOH, H 2 O/dioxane. C) Synthesis of Mmt monomers from the corresponding Boc monomers.…”