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Abstract Triplex-forming peptide nucleic acids (PNAs) require chemical modifications for efficient sequence-specific recognition of DNA and RNA at physiological pH. Our research groups have developed 2-aminopyridine (M) as an effective mimic of protonated cytosine in C+•G-C triplets. M-modified PNAs have a high binding affinity and sequence specificity as well as promising biological properties for improving PNA applications. This communication reports the optimization of synthetic procedures that give PNA M monomer in seven steps, with minimal need for column chromatography and in good yields and high purity. The optimized route uses inexpensive reagents and easily performed reactions, which will be useful for the broad community of nucleic acid chemists. Thought has also been given to the potential for future development of industrial syntheses of M monomers.
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This content will become publicly available on March 4, 2026
2-Aminopyridine nucleobases enable DNA invasion by peptide nucleic acid clamps under physiological conditions
Peptide nucleic acid (PNA) clamps modified with 2-aminopyridine (M) nucleobase invaded double-stranded DNA under physiological salt conditions. In contrast, PNAs carrying common nucleobases could not fully invade DNA under these conditions. M-modified PNAs may overcome the problematic requirement for low salt concentration, a long-standing DNA invasion problem.
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- PAR ID:
- 10616061
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 61
- Issue:
- 20
- ISSN:
- 1359-7345
- Page Range / eLocation ID:
- 4070 to 4073
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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