1. High-affinity peptide nucleic acid oligomers containing tricyclic cytosine analogues
Kallanthottathil G Rajeev, Martin A Maier, Elena A Lesnik, Muthiah Manoharan Org Lett. 2002 Dec 12;4(25):4395-8. doi: 10.1021/ol027026a.
[structure: see text] Peptide nucleic acid (PNA) monomers containing the tricyclic cytosine analogues phenoxazine, 9-(2-aminoethoxy)phenoxazine (G-clamp), and 9-(3-aminopropoxy)phenoxazine (propyl-G-clamp) have been synthesized. The modified nucleobases were incorporated into PNA oligomers using Boc-chemistry for solid-phase synthesis. PNAs containing single G-clamp modifications exhibit significantly enhanced affinity toward RNA and DNA targets relative to unmodified PNA while maintaining mismatch discrimination. These PNA G-clamp modifications exhibit the highest increase in affinity toward nucleic acid targets reported so far for PNA modifications.
2. Peptide-nucleic acids (PNAs) with pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a universal base: their synthesis and binding affinity for oligodeoxyribonucleotides
Taisuke Hirano, Kenji Kuroda, Masanori Kataoka, Yoshihiro Hayakawa Org Biomol Chem. 2009 Jul 21;7(14):2905-11. doi: 10.1039/b821193k. Epub 2009 May 27.
Peptide-nucleic acids (PNAs) including pyrimido[4,5-d]pyrimidine-2,4,5,7-(1H,3H,6H,8H)-tetraone (PPT) as a nucleobase were synthesized, and their binding affinity for the complementary oligodeoxyribonucleotides was investigated. We found that PNAs with one or two PPT(s) and natural nucleobases (i.e., adenine, cytosine, guanine, or thymine) have excellent binding affinity for oligodeoxyribonucleotides with complementary bases at the positions facing the natural nucleobases, and with adenine, cytosine, guanine, and thymine at the positions opposite PPT in PNAs. The binding affinity of the PPT-containing PNA is higher than or comparable to that of a PNA consisting of all complementary natural nucleobases, viz. a PNA with a suitable natural nucleobase in place of PPT in the PPT-containing PNA. Consequently, it was concluded that PPT serves as a useful universal base that can recognize all natural nucleobases.
3. Amino/guanidino-functionalized N-(pyrrolidin-2-ethyl)glycine-based pet-PNA: design, synthesis and binding with DNA/RNA
Sachin S Gokhale, Vaijayanti A Kumar Org Biomol Chem. 2010 Aug 21;8(16):3742-50. doi: 10.1039/c004005c. Epub 2010 Jun 10.
The N-(pyrrolidin-2-ethyl) glycine-based PNA (pet-PNA) backbone, with 4-amino or 4-guanidino-functionalized pyrrolidine ring, confers constrained conformational flexibility on aegPNA. The oligomers bind to the target DNA and RNA sequences with increased sequence specificity and antiparallel versus parallel orientation selectivity. The easy post-synthetic guanidination gives very good access to the positively charged PNA oligomers.
