A convenient automated solid-phase synthesis of PNA-(5′)-DNA-(3′)-PNA chimera

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

“…Acylation of Mmt-Aeg-OMe with chloroacetyl chloride in THF, gives a chloroacetyl derivative that can be used, after solvent exchange from THF to DMF, to alkylate thymine directly. A further synthetic route (Figure 8 C), reported by van der Laan et al [33,34] and Finn et al [24] , gives the Mmt-Aeg-esters by a Boc to Mmt ªprotecting group exchangeº, starting from the Boc-Aegesters. After saponification the monomers are converted into their tetrabutylammonium or pyridinium salts.…”

“…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.…”

“…C) Synthesis of Mmt monomers from the corresponding Boc monomers. [24,33,34] D) Synthesis of Mmt monomers via intermediates which can be precipitated: [22] ing groups established in oligonucleotide synthesis, such as the benzoyl-, anisoyl-, and tert-butyl benzoyl-groups for cytosine and adenine, or the isobutyryl-and acetyl-groups for guanine, are especially suitable in this context. The synthesis of these monomers, which are universally applicable for the synthesis of PNAs and PNA/DNA chimeras, is shown in Figures 8 A ± C. The synthetic route [26] we follow utilizes TOTU [35] to couple the nucleobase acetic acids to Mmt-Aeg-OMe.…”

Hybridization and Melting Behavior of Peptide Nucleic Acid (PNA) Oligonucleotide Chimeras Conjugated to Gold Nanoparticles

“…The synthesis of PNA-DNA chimeras 3 and 4 were performed using the methodology described previously [24][25][26][27]. In this strategy the monomethoxytrityl (MeOTr) group is used for the temporary protection of the backbone amino function and acyl protecting groups are used for the protection of the exocyclic amino functions of the nucleobases [24][25][26][27].…”

“…In this strategy the monomethoxytrityl (MeOTr) group is used for the temporary protection of the backbone amino function and acyl protecting groups are used for the protection of the exocyclic amino functions of the nucleobases [24][25][26][27]. The MeOTr is removed under mild conditions (3% trichloroacetic acid in dichloromethane), and the nucleobase protecting groups are removed using concentrated aqueous ammonia.…”