Selective Transcription of an Unnatural Naphthyridine:Imidazopyridopyrimidine Base Pair Containing Four Hydrogen Bonds with T7 RNA Polymerase

• Published in: Angewandte Chemie International Edition Vol. 53; no. 47; pp. 12844 - 12848
• Main Authors: Nomura, Yusaku, Kashiwagi, Satoshi, Sato, Kousuke, Matsuda, Akira
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.11.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Base Pairing; Biocatalysis; Chemistry; Chemistry, Multidisciplinary; Deoxyribonucleic acid; DNA polymerase; DNA-Directed RNA Polymerases - metabolism; Genes; Human; Humans; Hydrogen Bonding; Hydrogen bonds; Molecular Structure; Naphthyridines - chemistry; Naphthyridines - metabolism; nucleobases; nucleotides; Physical Sciences; Polymerase; Pyrimidines - chemistry; Pyrimidines - metabolism; Ribonucleic acids; RNA polymerase; RNA recognition; Science & Technology; Synthesis; unnatural base pairs; Viral Proteins - metabolism; OLIGODEOXYNUCLEOTIDES; NUCLEOTIDE INCORPORATION; RNA recognition; CRYSTAL-STRUCTURES; DNA-POLYMERASE; hydrogen bonds; REPLICATION; nucleobases; STRUCTURAL BASIS; HYDROPHOBIC BASE; GENETIC ALPHABET; ENZYMATIC INCORPORATION; SITE-SPECIFIC INCORPORATION; nucleotides; unnatural base pairs
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201406402

The naphthyridine:imidazopyridopyrimidine base pair is the first base pair containing four hydrogen bonds that can be replicated selectively and efficiently by the use of DNA polymerases. Herein we describe the synthesis of naphthyridine‐C‐ribonucleoside 5′‐triphosphate (rNaTP) and transcription reactions catalyzed by T7 RNA polymerase with rNaTP and template DNA containing imidazopyridopyrimidine. The transcription reaction was also applied to a longer transcript containing part of the human c‐Ha‐Ras gene. Four to be sure: The naphthyridine (Na):imidazopyridopyrimidine (Im) base pair containing four hydrogen bonds replicates selectively and efficiently under the action of DNA polymerases. Naphthyridine‐C‐ribonucleoside 5′‐triphosphate (rNaTP) was transcribed successfully opposite a template DNA containing the Im base by T7 RNA polymerase. The transcription reaction was also applied to a longer transcript containing a part of the human c‐Ha‐Ras gene.