Abstract
The synthesis of N-((N4-(benzoyl)cytosine-1-yl)acetyl)- N -(2-Boc-aminoethyl)glycine (CBz) and the incorporation of this monomer into PNA oligomers are described. A single CBzresidue within a 10mer homopyrimidine PNA is capable of switching the preferred binding mode from a parallel to an antiparallel orientation when targeting a deoxyribonucleotide sequence at neutral pH. The resulting complex has a thermal stability equal to that of the corresponding PNA-DNA duplex, indicative of a strong destabilization of Hoogsteen strand PNA binding due to steric interference by the benzoyl moieties. Accordingly, incorporation of the CBz residue into linked PNAs (bis-PNAs) results in greatly reduced thermal stability of the formed PNA:DNA complexes. Thus, incorporation of the CBz monomer could eliminate the stability bias of triplex-forming sequences in PNA used in hybridization arrays and combinatorial library formats. Furthermore, it is shown that the benzoyl moiety does not severely interfere with Watson-Crick hydrogen bonding, thereby presenting an interesting route for novel cytosine modifications.
| Original language | English |
|---|---|
| Journal | Nucleic Acids Research |
| Volume | 26 |
| Issue number | 11 |
| Pages (from-to) | 2735-9 |
| Number of pages | 5 |
| ISSN | 0305-1048 |
| Publication status | Published - 1 Jun 1998 |
Keywords
- Benzoates
- Cytosine/analogs & derivatives
- Oligonucleotides/chemical synthesis
- Peptides/chemical synthesis