Synthetic,Structural, and RNA Binding Studies on 2-Aminopyridine-Modified Triplex-Forming Peptide Nucleic Acids

The development of new RNA-binding ligands is attracting increasing interest in fundamental science and the pharmaceutical industry. The goal of this study was to improve the RNA binding properties of triplex-forming peptide nucleic acids (PNAs) by further increasing the pK_a of 2-aminopyridine ( M ). Protonation of M was the key for enabling triplex formation at physiological pH in earlier studies. Substitution on M by an electron-donating 4-methoxy substituent resulted in slight destabilization of the PNA–dsRNA triplex, contrary to the expected stabilization due to more favorable protonation. To explain this unexpected result, the first NMR structural studies were performed on an M -modified PNA–dsRNA triplex which, combined with computational modeling identified unfavorable steric and electrostatic repulsion between the 4-methoxy group of M and the oxygen of the carbonyl group connecting the adjacent nucleobase to PNA backbone. The structural studies also provided insights into hydrogen-bonding interactions that might be responsible for the high affinity and unusual RNA-binding preference of PNAs.     

From Peptide Nucleic Acids to Supramolecular Structures of Nucleic Acid Derivatives

Nucleic acids play a pivotal role in life processes. The endeavours to shed light on the essential properties of these intriguing building blocks led us to the synthesis of different analogues and the investigation of their properties. First various peptide nucleic acid monomers and oligomers have been synthesized, using an Fmoc/acyl protecting group strategy, and their properties studied. The serendipitous discovery of a side reaction of coupling agents led us to the elaboration of a peptide sequencing method. The capricious behaviour of guanine derivatives spurred the determination of their substitution pattern using ¹³C, ¹⁵N NMR, and mass spectrometric methods. The properties of guanines initiated the logical transition to the study of supramolecular systems composed of purine analogues. Thus, xanthine and uracil derivatives have been obtained and their supramolecular self-assembly properties scrutinized in gas, solid, and liquid states and at solid-liquid interfaces.     

卟啉化合物与核酸的相互作用研究

本文综述了卟啉化合物与核酸相互作用时的结合模式、光谱方法和重要的应用研究, 并对该领域的研究前景作了展望。     

PNA: Synthetic Polyamide Nucleic Acids with Unusual Binding Properties

The astonishing discovery that peptide nucleic acids (PNAs, B=nucleobase), in spite of their drastic structural difference to natural DNA, are better nucleic acid mimetics than many other oligonucleotides has resulted in an explosion of research into this class of compounds. The synthesis, physical properties, and biological interactions of PNAs as well as their chimeras with DNA and RNA are summarized here.     

喹哪啶蓝与核酸作用的光谱研究及分析

外部堆积结合;分光光度法;喹哪啶蓝与核酸作用的光谱研究及分析     

小分子与核酸相互作用的研究进展

评述了小分子与核酸相互作用的结合模式和研究方法。引用文献59篇。     

Interactions of Night Blue with Nucleic Acids and Determination of Nucleic Acids Using Resonance Light Scattering Technique

The noncovalent interactions of night blue (NB) with several nucleic acids in buffer medium of Britton‐Robinson at pH 4.1 have been studied by spectroscopic methods. It is shown that the binding of NB with nucleic acids involves the J‐aggregation of NB molecules on the surface of nucleic acids. The aggregation was encouraged by polyanions nucleic acids, in which nucleic acids served for acting templates. In this connection, a new method of nucleic acids with sensitivity at nanogram level is proposed based on the measurement of enhanced resonance light scattering (RLS). The linear range of ctDNA, fsDNA and yRNA is 0.01—2.5, 0.03—2.5 and 0.04—1.0 μg/mL, respectively, and the corresponding detection limits (3s?) are 9.4, 7.3 and 5.7 ng/mL at 2.5 × 10–⁵mol/L of NB. Synthetic and real samples were analyzed with satisfactory results.     

Interactions of Safranin T with Nucleic Acids

The interactions of Safranin T (ST) with several nucleic acids have been investigated by electrochemical, UV‐visible and CD spectroscopic techniques. The form of the nucleic acid‐ST complexes is sensitive to the ratio of the two species. Two electrochemically inactive complexes such as, nucleic acid‐ST and nucleic acid‐2ST, were formed while ST interacts with nucleic acids. Two processes were obtained from spectral experiments: (1) at the high value of R (R is defined as the ratio of the total concentration of ST to that of nucleic acid), ST is groove‐binding with stacking, (2) at the low value of R, ST is groove‐binding without stacking. Intrinsic binding constants were obtained by spectral methods. The experiments also show that electrostatic binding plays an important role in the interaction of ST with nucleic acids.     

多核配合物与核酸作用的研究

综述了近年来各种多核金属配合物与核酸作用的研究,作为抗肿瘤药物、核酸探针、核酸切割剂等的应用概况。计论了结构与作用机理之间的关系。     

Intercalating Nucleic Acids Containing Insertions of Naphthalimide

In a study of linker‐length dependence, we evaluated naphthalimide (= 1H‐benzo[de]isoquinoline‐1,3(2H)‐dione) and 4‐bromonaphthalimide as intercalating nucleic acids. We used a vicinal dihydroxy system when incorporating the six different naphthalimide monomers into DNA, and found the minimum linker‐length to be five C‐atoms. With this length of the linker, naphthalimide was discriminating between DNA and RNA – stabilizing DNA, while destabilizing RNA. Furthermore, naphthalimide showed universal base character by hybridizing to the four natural bases with a range as narrow as 1.4°. When compared to pyrene, naphthalimide with the same linker‐length gave significantly higher thermal meltings when hybridized to DNA.     

Selective Chemical Modification to the Higher-Order Structures of Nucleic Acids

DNA and RNA can adopt a variety of stable higher-order structural motifs, including G-quadruplex (G4 s), mismatches, and bulges. Many of these secondary structures are closely related to the regulation of gene expression. Therefore, the higher-order structure of nucleic acids is one of the candidate therapeutic targets, and the development of binding molecules targeting the higher-order structure of nucleic acids has been pursued vigorously. Furthermore, as one of the methodologies for detecting the higher-order structures of these nucleic acids, developing techniques for the selective chemical modification of the higher-order structures of nucleic acids is also underway. In this personal account, we focus on the following higher-order structures of nucleic acids, double-stranded DNA containing the abasic site, T−T/U−U mismatch structure, and G-quadruplex structure, and describe the development of molecules that bind to and chemically modify these structures.     

Tellurium-Modified Nucleosides,Nucleotides, and Nucleic Acids with Potential Applications

Tellurium was successfully incorporated into proteins and applied to protein structure determination through X-ray crystallography. However, studies on tellurium modification of DNA and RNA are limited. This review highlights the recent development of Te-modified nucleosides, nucleotides, and nucleic acids, and summarizes the main synthetic approaches for the preparation of 5-PhTe, 2′-MeTe, and 2′-PhTe modifications. Those modifications are compatible with solid-phase synthesis and stable during Te-oligonucleotide purification. Moreover, the ideal electronic and atomic properties of tellurium for generating clear isomorphous signals give Te-modified DNA and RNA great potential applications in 3D crystal structure determination through X-ray diffraction. STM study also shows that Te-modified DNA has strong topographic and current peaks, which immediately suggests potential applications in nucleic acid direct imaging, nanomaterials, molecular electronics, and diagnostics. Theoretical studies indicate the potential application of Te-modified nucleosides in cancer therapy.     

Orthogonal Synthesis of Xeno Nucleic Acids

Sequence‐defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid‐phase orthogonal “AB+CD” iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper‐catalyzed azide–alkyne cycloaddition (CuAAC) and acid–amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks).     

基于核酸分子识别的电化学分析方法与应用

核酸作为生物体遗传信息的载体以及分子生物学和生物分析化学中重要的功能分子,近年来在电化学分析中受到了越来越多的重视。本文以作者所在研究组的工作为实例,对核酸分子识别的电化学分析方法作出简要的评述,内容涉及核酸序列和基因变异的电化学分析以及核酸作为功能分子进行识别检测的电化学分析等等。     

核酸分子嵌入剂

求文对核酸分子嵌入剂在核酸的识别、分离及分析中的应用，嵌入剂在特效新药设计及对核酸序列的特异位点裂解方面的新成就进行了评述。讨论了嵌入剂与溶液中ＤＮＡ及固定于ＮＣ膜上的单链ＤＮＡ的作用机理，引用参考文献３２篇。     

Noncovalent Helicene Structure between Nucleic Acids and Cyanuric Acid

Cyanuric acid (CA), a triazine heterocycle, is extensively utilized for noncovalent self-assembly. The association between poly(adenine) and CA into micron-length fibers was a remarkable observation made by Sleiman and co-workers, who proposed that adenine and CA adopt a hexameric rosette configuration in analogy with previously reported structures for CA assemblies. However, recent experimental observations from the Krishnamurthy group led to a reevaluation of the hexameric rosette model, wherein they have proposed a hydrogen-bonded helicene model as an alternative. Our molecular dynamics simulations show that the hexad model is indeed unlikely and that this novel noncovalent helicene geometry, where the adenine and CA bases form an extended helical hydrogen-bond network across the system, is a more probable structural motif. The existence of noncovalent helicene compounds may have wide-ranging applications in DNA nanotechnology and helicene chemistry.