Substituted 1,8-Naphthyridin-2(1H)-ones Are Superior to Thymine in the Recognition of Adenine in Duplex as Well as Triplex Structures
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- 作者：Anne B. Eldrup ; Caspar Christensen ; Gerald Haaima ; and Peter E. Nielsen
- 刊名：Journal of the American Chemical Society
- 出版年：2002
- 出版时间：April 3, 2002
- 年：2002
- 卷：124
- 期：13
- 页码：3254 - 3262
- 全文大小：103K
- 年卷期：v.124,no.13(April 3, 2002)
- ISSN：1520-5126
文摘
The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements forincorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplexnucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex(Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermalstability per modification was dependent on the sequence context, ranging from 2.0 
C (in separate positions)to 3.5 C (in adjacent positions) in PNA-DNA duplexes and from 1.2 C (in separate positions) to 3.2 C(in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employedto demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen)recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicatethat the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence ofsingle-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crickbase pairing within a helix.
C (in separate positions)to 3.5 C (in adjacent positions) in PNA-DNA duplexes and from 1.2 C (in separate positions) to 3.2 C(in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employedto demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen)recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicatethat the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence ofsingle-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crickbase pairing within a helix.