α-L-LNA（α-L-核糖构型锁定核酸）对DNA的识别：一项核磁共振光谱研究。
alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) recognition of DNA: an NMR spectroscopic study.
作者信息
Nielsen Katrine M Ellemann, Petersen Michael, Håkansson Anders E, Wengel Jesper, Jacobsen Jens Peter
机构信息
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Odense University, 5230 Odense M, Denmark.
出版信息
Chemistry. 2002 Jul 2;8(13):3001-9. doi: 10.1002/1521-3765(20020703)8:13<3001::AID-CHEM3001>3.0.CO;2-1.
We have used NMR and CD spectroscopy to study and characterise two alpha-L-LNA:DNA duplexes, a nonamer that incorporates three alpha-L-LNA nucleotides and a decamer that incorporates four alpha-L-LNA nucleotides, in which alpha-L-LNA is alpha-L-ribo-configured locked nucleic acid. Both duplexes adopt right-handed helical conformations and form normal Watson-Crick base pairing with all nucleobases in the anti conformation. Deoxyribose conformations were determined from measurements of scalar coupling constants in the sugar rings, and for the decamer duplex, distance information was derived from 1H-1H NOE measurements. In general, the deoxyriboses in both of the alpha-L-LNA:DNA duplexes adopt S-type (B-type structure) sugar puckers, that is the inclusion of the modified alpha-L-LNA nucleotides does not perturb the local native B-like double-stranded DNA (dsDNA) structure. The CD spectra of the duplexes confirm these findings, as these display B-type characteristic features that allow us to characterise the overall duplex type as B-like. The 1H-1H NOE distances which were determined for the decamer duplex were employed in a simulated annealing protocol to generate a model structure for this duplex, thus allowing a more detailed inspection of the impact of the alpha-L-ribo-configured nucleotides. In this structure, it is evident that the malleable DNA backbone rearranges in the vicinity of the modified nucleotides in order to accommodate them and present their nucleobases in a geometry suitable for Watson-Crick base pairing.
我们利用核磁共振（NMR）和圆二色（CD）光谱对两个α-L-锁核酸（LNA）:DNA双链体进行了研究和表征，一个是包含三个α-L-LNA核苷酸的九聚体，另一个是包含四个α-L-LNA核苷酸的十聚体，其中α-L-LNA是α-L-核糖构型的锁核酸。两个双链体均采用右手螺旋构象，并与所有处于反式构象的核碱基形成正常的沃森-克里克碱基对。通过测量糖环中的标量耦合常数确定脱氧核糖构象，对于十聚体双链体，距离信息来自1H-1H NOE测量。一般来说，两个α-L-LNA:DNA双链体中的脱氧核糖均采用S型（B型结构）糖环构象，也就是说，引入修饰的α-L-LNA核苷酸不会干扰局部天然的B样双链DNA（dsDNA）结构。双链体的CD光谱证实了这些发现，因为它们显示出B型特征，使我们能够将整体双链体类型表征为B样。为十聚体双链体确定的1H-1H NOE距离用于模拟退火程序，以生成该双链体的模型结构，从而能够更详细地考察α-L-核糖构型核苷酸的影响。在这个结构中，很明显，具有可塑性的DNA主链在修饰核苷酸附近重新排列，以容纳它们，并使它们的核碱基呈现出适合沃森-克里克碱基配对的几何形状。
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