Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a D-lysine-based chiral PNA-DNA duplex
Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a D-lysine-based chiral PNA-DNA duplex
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DOI：
10.1073/pnas.2034746100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Pedone, C
中科院分区：
文献类型：
--
作者：
Menchise, V;De Simone, G;Pedone, C
肽核酸（PNAs）是寡核苷酸类似物，其中糖-磷酸骨架已被假肽骨架取代。它们以高特异性和选择性结合DNA和RNA，导致PNA-RNA和PNA-DNA杂合体比相应的核酸复合物更稳定。PNA对核酸的结合亲和力和选择性可以通过将立体中心（例如基于D-Lys的单元）引入PNA骨架中来修饰。为了研究手性PNAs的结构特征，通过溴代衍生物的单波长反常衍射实验，在1.66埃分辨率下解析了含有三个D-Lys基单体（即H-GpnTpnApnGpnAdlTdlCdlApnCpnTpn-NH 2，其中pn代表假肽连接，dl代表D-Lys类似物）与互补反平行DNA杂交的PINA十聚体的结构.基于D-Lys的手性PNA-DNA（LPD）异源双链体采用所谓的P-螺旋构象。从LPD中的PNA构象与在其他PNA结构中观察到的构象之间的实质性相似性，可以得出结论，PNA具有对P-螺旋的固有构象偏好，并且它们的灵活性相当有限。PNA的构象刚性通过手性中心的存在而增强，限制了PNA链采用其他构象的能力，并最终增加了分子识别的选择性。
Peptide nucleic acids (PNAs) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton. They bind DNA and RNA with high specificity and selectivity, leading to PNA-RNA and PNA-DNA hybrids more stable than the corresponding nucleic acid complexes. The binding affinity and selectivity of PNAs for nucleic acids can be modified by the introduction of stereogenic centers (such as D-Lys-based units) into the PNA backbone. To investigate the structural features of chiral PNAs, the structure of a PINA decamer containing three D-Lys-based monomers (namely H-GpnTpnApnGpnAdlTdlCdlApnCpnTpn-NH2, in which pn represents a pseudopeptide link and dl represents a D-Lys analogue) hybridized with its complementary antiparallel DNA has been solved at a 1.66-Angstrom resolution by means of a sing le-wavelength anomalous diffraction experiment on a brominated derivative. The D-Lys-based chiral PNA-DNA (LPD) heteroduplex adopts the so-called P-helix conformation. From the substantial similarity between the PNA conformation in LPD and the conformations observed in other PNA structures, it can be concluded that PNAs possess intrinsic conformational preferences for the P-helix, and that their flexibility is rather restricted. The conformational rigidity of PNAs is enhanced by the presence of the chiral centers, limiting the ability of PNA strands to adopt other conformations and, ultimately, increasing the selectivity in molecular recognition.