1,8-Naphthyridin-2(1H)-ones − Novel Bicyclic and Tricyclic Analogues of Thymine in Peptide Nucleic Acids (PNAs)

✍ Scribed by Anne B. Eldrup; Bettina B. Nielsen; Gerald Haaima; Hanne Rasmussen; Jette S. Kastrup; Caspar Christensen; Peter E. Nielsen

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 402 KB
• Volume: 2001
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/1099-0690(200105)2001:9<1781::aid-ejoc1781>3.0.co;2-k

✦ Synopsis

The synthesis of two novel PNA nucleobases derived from 1,8-naphthyridin-2(1H)-one (bT) and benzo[b]-1,8-naphthyridin-2(1H)-one (tT) are reported, together with their incorporation into oligomers of PNA and evaluation as substitutes for thymine. Compound bT is shown to be an effective mimic of the natural thymine nucleobase in PNA-DNA, PNA-RNA, and PNA-PNA duplex structures. A study using singly mismatched target sequences showed bT to be selective for the recognition of adenine. The X-ray structure of a PNA hexamer containing a single bT base (H-GbTATAC-L-lys-NH 2 ) was determined to 1.8 A ˚resolution and confirmed the basepairing capability with adenine. The introduction of a bT base does not alter the P-form double helix structure of PNA, as compared to other PNA structures containing natural nucleobases. With the tricyclic derivative, incorporation of sev-