New β-cyclodextrin derivatives possessing biologically active saccharide antennae

Abstract

The synthesis of monosubstituted β-cyclodextrin derivatives having the monosaccharides, β-D-glucose, β-D-galactose, α-D-mannose, β-L and β-D-fucose linked to the macrocycle via a C9 spacer chain is described. The approach is based on the highly efficient coupling of the NCS sugar derivatives to monomethyl nonanedicarboxylate to generate a stable amido linkage. The NMR studies show the saccharide antennae to be oriented into the environment and not towards the CD cavity.     

基于小分子的核酸结构探针最新研究进展

本文主要综述了基于小分子的核酸结构探针的最新研究进展.所探索的核酸结构主要有四链核酸（包括G-四链体以及i-motif）结构、三链核酸结构、左手螺旋DNA结构以及不规则核酸结构（包括突起结构以及环状结构）等;所探索的小分子包括过渡金属配合物、大环共轭化合物、环肽以及寡糖抗生素等.     

Z-DNA-induced super-transport of energy within genomes

Spontaneous transitions of genomic DNA segments from right-handed B-DNA into the left-handed, high-energy Z conformation are unstable within topologically relaxed DNA molecules, such as mammalian chromosomes. Here we show, from direct application of the principles of statistical physics with a promoter region in the mouse genome as a representative example, that the life span for this alternate DNA conformation may be much smaller than the characteristic time of thermal fluctuations that cause the B-to-Z transition. Surprisingly, such a short existence of Z-DNA is important because it can be responsible for super-transport of energy within a genome. This type of energy transport can be utilized by a cell to communicate information about the state of particular chromatin domains within chromosomes or as a buffer against genome instability.     

镍离子对DNA结构和导电性的影响

在碱性环境下,向DNA溶液中加入较低浓度的镍离子制备了金属DNA （M-DNA）,并分别对单根DNA和M-DNA的导电性进行了测量.结果表明,二者均表现出半导体性质;随镍离子浓度的增加导电性明显增强,伏特间隙减小;当镍离子浓度超过0.1 mmol/L时,DNA的电导几乎不随镍离子浓度变化.在中性环境下向DNA溶液中加入较高浓度的镍离子,实现了DNA从右手到左手螺旋结构的转变.利用STM观察到了左手螺旋结构的Z-DNA,Z构象可以分辨出大沟与小沟,并且螺旋结构不均匀,伴有局部的解旋和无序化;单根Z-DNA的导电性明显减弱.DNA,M-DNA,Z-DNA的电导大小关系为G_M-DNA>G_DNA>G_Z-DNA.通过紫外吸收和Raman光谱测量发现,使DNA发生右手到左手螺旋结构转变的镍离子浓度约为1.7 mol/L. 关键词： 镍离子 M-DNA Z-DNA 导电性     

Short but Weak: The Z‐DNA Lone‐Pair⋅⋅⋅π Conundrum Challenges Standard Carbon Van der Waals Radii

Current interest in lone‐pair???π (lp???π) interactions is gaining momentum in biochemistry and (supramolecular) chemistry. However, the physicochemical origin of the exceptionally short (ca. 2.8 Å) oxygen‐to‐nucleobase plane distances observed in prototypical Z‐DNA CpG steps remains unclear. High‐level quantum mechanical calculations, including SAPT2+3 interaction energy decompositions, demonstrate that lp???π contacts do not result from n→π* orbital overlaps but from weak dispersion and electrostatic interactions combined with stereochemical effects imposed by the locally strained structural context. They also suggest that the carbon van der Waals (vdW) radii, originally derived for sp³ carbons, should not be used for smaller sp² carbons attached to electron‐withdrawing groups. Using a more adapted carbon vdW radius results in these lp???π contacts being no longer of the sub‐vdW type. These findings challenge the whole lp???π concept that refers to elusive orbital interactions that fail to explain short interatomic contact distances.     

Short but Weak: The Z-DNA Lone-Pair⋅⋅⋅π Conundrum Challenges Standard Carbon Van der Waals Radii

Current interest in lone-pair⋅⋅⋅π (lp⋅⋅⋅π) interactions is gaining momentum in biochemistry and (supramolecular) chemistry. However, the physicochemical origin of the exceptionally short (ca. 2.8 Å) oxygen-to-nucleobase plane distances observed in prototypical Z-DNA CpG steps remains unclear. High-level quantum mechanical calculations, including SAPT2+3 interaction energy decompositions, demonstrate that lp⋅⋅⋅π contacts do not result from n→π* orbital overlaps but from weak dispersion and electrostatic interactions combined with stereochemical effects imposed by the locally strained structural context. They also suggest that the carbon van der Waals (vdW) radii, originally derived for sp³ carbons, should not be used for smaller sp² carbons attached to electron-withdrawing groups. Using a more adapted carbon vdW radius results in these lp⋅⋅⋅π contacts being no longer of the sub-vdW type. These findings challenge the whole lp⋅⋅⋅π concept that refers to elusive orbital interactions that fail to explain short interatomic contact distances.     

DNA中的B-Z"链接"

DNA能够通过改变自身的构象来完成它在生命过程中的一些重要作用。在进行转录和其它一些生理过程中,B-DNA的局部区域会转变为Z-DNA,形成具有两个B-Z接合点的奇特的B-DNA-Z-DNA-B-DNA结构,在每个接合点处有一对碱基的氢键发生断裂且碱基被挤出而连接在双螺旋的外侧。探讨这种结构的形成机制对于理解DNA的结构与功能的关系具有重要意义,也将有助于更深刻地认识Z-DNA所扮演的角色。     

Exact Solutions of the Equilibrium Shape Equations in a General WLC Model for DNA Forms

In this letter,we are going to use a geometrical approach to describe the free energy of DNA structures.The exact solutions of the equilibrium shape equations in a general WLC model for DNA forms by using the Feoli's formalism [A.Feoli,et al.,Nucl.Phys.B 705(2005) 577] are studied.Then,the free energy of transition between Band Z-DNA is calculated in this formalism.     

Construction of ssDNA-Attached LR-Chimera Involving Z-DNA for ZBP1 Binding Analysis

The binding of proteins to Z-DNA is hard to analyze, especially for short non-modified DNA, because it is easily transferred to B-DNA. Here, by the hybridization of a larger circular single-stranded DNA (ssDNA) with a smaller one, an LR-chimera (involving a left-handed part and a right-handed one) with an ssDNA loop is produced. The circular ssDNAs are prepared by the hybridization of two ssDNA fragments to form two nicks, followed by nick sealing with T4 DNA ligase. No splint (a scaffold DNA for circularizing ssDNA) is required, and no polymeric byproducts are produced. The ssDNA loop on the LR-chimera can be used to attach it with other molecules by hybridization with another ssDNA. The gel shift binding assay with Z-DNA specific binding antibody (Z22) or Z-DNA binding protein 1 (ZBP1) shows that stable Z-DNA can form under physiological ionic conditions even when the extra ssDNA part is present. Concretely, a 5′-terminal biotin-modified DNA oligonucleotide complementary to the ssDNA loop on the LR-chimera is used to attach it on the surface of a biosensor inlaid with streptavidin molecules, and the binding constant of ZBP1 with Z-DNA is analyzed by BLI (bio-layer interferometry). This approach is convenient for quantitatively analyzing the binding dynamics of Z-DNA with other molecules.