光控CRISPR技术的研究进展

成簇规则间隔短回文重复序列和成簇规则间隔短回文重复序列相关(CRISPR-Cas)系统提供了用于可编程基因组编辑的多功能工具. CRISPR与光遗传学及光化学生物学技术的结合产生了很多新的成果. 光激活的CRISPR-Cas系统能够在空间和时间上更好地调控RNA引导的核酸酶的活性. 近年来, 科学家结合CRISPR和多种光学技术, 开发出了一系列光激活的CRISPR工具. 这些工具让研究人员能够在空间、 时间和基因组坐标上进行高分辨率的生命活动研究. 本文概述了CRISPR系统、 基因编辑技术、 光遗传学和光化学生物学的研究进展, 并对光诱导的CRISPR技术的发展进行了展望.     

光笼分子与材料研究进展

光笼(photocage)是一种用于光控释放的光敏物质,是以物理和化学等方法将目标释放物与光敏基团及其他功能基团结合形成的对光敏感的物质,在指定波段的光照射线下,光笼能够实现目标物的可控释放.因其具备时空调控、操作简单、易于控制、可修饰性强和对机体损伤小等优点,使其广泛应用在化学、生物学、材料学和医学等领域.本综述介绍...     

环状寡聚核苷酸的研究进展

环状结构的核酸因其首尾相连的特殊结构,可提高其对核酸外切酶的稳定性,并且其环状结构可使其具有特殊的功能.早期由于检测技术的限制,研究者对环状核酸的研究相对较少.近年来,随着科学技术的进步,研究者发现生物体内存在各种环状核酸,并具有独特的生理调节功能.对于较小的环状寡聚核苷酸(几十个碱基)在生命体中是否存在以及其可能的功能仍未知晓.本文综述了环状核酸(特别是较小环的寡聚核苷酸)主要的两类合成法(酶合成法和化学合成法),并比较了它们各自的优缺点.同时阐述了各种环状功能核酸的结构特性以及它们对特定生物活性和基因功能的特异性调控,为阐明环状核酸在生物体内的产生及其作用机制的化学生物学研究提供了新的研究工具.     

聚己内酰胺(尼龙-6)光降解与光敏化降解的研究

本工作通过对尼龙-6的荧光光谱和磷光光谱的研究,发现其中包含两种发光化学品类。一种是酰胺基团本身,它能给出有特征的荧光和磷光光谱,这种光谱提供了鉴定酰胺类化合物和聚合物的一种可能的手段。另一类是在聚合和纺丝过程中因热氧化而引入的各种杂质基团。这些杂质基团对于300-360nm波长的光十分敏感, 能迅速发生光化学变化, 从而引发尼龙的降解。     

偶氮苯作用的核酸开关在生物体内的可逆光调控

随着人们对偶氮苯分子光异构化机理和特性认识的深入,偶氮苯在核酸分子中的引入及其相关过程的可逆调控也受到了大量关注.偶氮苯分子作为光响应元件不仅用于合成智能材料或分子机器,而且正迅速渗透到化学生物学体系的分析和调控.考虑到核酸分子包含的信息多样性,小分子偶氮化合物引入到核酸分子中,可实现开关核酸的结构、RNA沉默、基因表达、适配体识别、酶活性等,也可用作核酸探针了解结构信息和分子之间的作用机理.因而,功能核酸的光可逆调控及其在生物领域中的应用,成为核酸化学领域的热门课题.本文主要阐述了偶氮苯与核酸结合的4种不同方式的设计原理及特点,通过筛选一些有代表性的例子,介绍偶氮苯类光敏分子的光异构化性能及其对核酸结构和功能的可逆调控在生物领域的研究进展,并列举出现阶段可能存在的问题,及对未来的发展前景进行展望.     

光调控分子有序聚集体及其功能化研究进展

双亲分子在溶液中可以缔合形成胶束、囊泡、液晶、乳液等有序分子聚集体。在分子中引入功能性的基团,通过改变分子的结构、浓度或引入外部刺激,可以对有序分子聚集体的类型和性能进行调控。光作为一种绿色可控的清洁能源,是一种理想的外部刺激信号。在双亲分子中引入感光基团,可以通过光照调节有序聚集体的组装,并进一步实现功能性的调控。本文综述了近年来在光调控分子有序聚集体方面的研究及其在生物、传导、纳米材料制备中的应用。同时,对光调控的功能性有序分子聚集体未来的发展前景进行了展望。     

高分子三重态敏化剂的研究IV: 高分子苯乙酮及其衍生物的光谱, 磷光量子产率及光敏化光稳定问题的研究

本工作合成和研究了高分子苯乙酮及其衍生物的光谱、磷光量子产率、磷光寿命以及光敏化、光稳定等问题。结量表明高分子光敏化剂和光稳定剂保持着它们原来相应小分子的光化学和光物理行为。高分子敏化剂由于T-T湮灭, 分子链中的光敏基团的存在一最佳值, 此时磷光量子产率最高, 敏化效率最好。但高分子光稳定剂则光稳定基团含量愈高光稳定能力愈强。     

高分子三重态敏化剂的研究IV: 高分子苯乙酮及其衍生物的光谱, 磷光量子产率及光敏化光稳定问题的研究

本工作合成和研究了高分子苯乙酮及其衍生物的光谱、磷光量子产率、磷光寿命以及光敏化、光稳定等问题。结量表明高分子光敏化剂和光稳定剂保持着它们原来相应小分子的光化学和光物理行为。高分子敏化剂由于T-T湮灭, 分子链中的光敏基团的存在一最佳值, 此时磷光量子产率最高, 敏化效率最好。但高分子光稳定剂则光稳定基团含量愈高光稳定能力愈强。     

高分子三重态敏化剂的研究——Ⅳ.高分子苯乙酮及其衍生物的光谱、磷光量子产率及光敏化光稳定问题的研究

本工作合成和研究了高分子苯乙酮及其衍生物的光谱、磷光量子产率、磷光寿命以及光敏化、光稳定等问题.结果表明高分子光敏化剂和光稳定剂保持着它们原来相应小分子的光化学和光物理行为.高分子敏化剂由于T-T湮灭,分子链中的光敏基团的含量存在一最佳值,此时磷光量子产率最高,敏化效率最好.但高分子光稳定剂则光稳定基团含量愈高光稳定能力愈强.     

基于光敏性胸腺嘧啶脱氧核苷亚膦酰胺单体的光响应DNA水凝胶

设计并合成了一种1-(4,5-二甲氧基-2-硝基苄基)乙氧基光敏基团保护的胸腺嘧啶脱氧核苷亚膦酰胺单体,将其通过固相合成引入到DNA序列中,可以实现对DNA链互补配对的光学调控;并进一步利用该单体合成了功能性的核酸序列,成功制备了快速光响应的DNA超分子水凝胶.该结果拓展了DNA单体的多样性,为构建新型光响应功能体系提...     

3-Nitro-2-naphthalenemethanol: a photocleavable protecting group for carboxylic acids

Photocleavable protecting groups are important in synthesis and caging. Among many such groups, 2-nitrobenzyl and related groups have been found useful in many applications. However, most of the known 2-nitrobenzyl-based caging chromophores show either low quantum yield or the photolysis wavelength is not suitable for various applications. In this paper, we report 2-nitro-3-naphthalenemethanol (NNM) as an efficient photocleavable protecting group for molecules containing a carboxylic function. NNM possesses photochemical properties better than the 2-nitrobenzyl chromophores as it is photoactivatable at 380 nm in aqueous medium (CH₃CN/H₂O, 3:2 v/v) showing the desired photochemistry. The carboxylic acids are efficiently photoreleased from NNM-based esters in almost quantitative yield.     

ON THE PHOTOSENSITIZING PROPERTIES OF N-FORMYLKYNURENINE AND RELATED COMPOUNDS

Abstract— The photochemical and photosensitizing properties of N -formylkynurenine (FK) and related compounds have been investigated using the laser flash photolysis technique by exciting water solutions with 265 nm or 353 nm radiation. The FK molecules in their first excited singlet state readily react with water leading probably to OH formation. FK triplet state reacts with many biological compounds including vitamins, amino acids and nucleic acid bases. The semi-reduced FK thus formed can, in turn, reduce substrates such as cytochrome c or O₂.     

光敏开关及其在化学生物学中的应用*

近年来随着生物医学技术的发展,人们需要越来越细致地在分子水平上研究各种生命过程。为了能够实现实时原位地观察活细胞或组织中的生命化学过程,需要使用以物理方法来选择性激活的分子探针。以共聚焦激光技术为基础的光敏开关能很好地解决这一问题。迄今,发展和用于光敏开关的光敏剂已成为化学生物学研究的重要方向。本文重点总结了各种可应用于共聚焦激光系统的单、双光子光敏基团（单光子的光敏基团主要有：硝基苯类、香豆素类等;双光子光敏基团主要有：香豆素类、喹啉类及吲哚衍生物类）以及这几类光敏基团在化学生物学中的应用。     

Biochemical and Biological Applications of Thermal Analysis

Thermoanalytical techniques, although not routinely used in biological investigations, when applied to biochemistry and biology have yielded some interesting results. Applications from which biologically interesting conclusions can be drawn have been reviewed. These include structural studies of biological membranes, lipoproteins, proteins and nucleic acids and studies of physiological processes such as membrane formation, depigmentation and adaptation to survive freezing stresses.     

Functional Xeno Nucleic Acids for Biomedical Application

Functional nucleic acids(FNAs) refer to a type of oligonucleotides with functions over the traditional genetic roles of nucleic acids, which have been widely applied in screening, sensing and imaging fields. However, the potential application of FNAs in biomedical field is still restricted by the unsatisfactory stability, biocompatibility, biodistribution and immunity of natural nucleic acids(DNA/RNA). Xeno nucleic acids(XNAs) are a kind of nucleic acid analogues with chemically modified sugar groups that possess improved biological properties, including improved biological stability, increased binding affinity, reduced immune responses, and enhanced cell penetration or tissue specificity. In the last two decades, scientists have made great progress in the research of functional xeno nucleic acids, which makes it an emerging attractive biomedical application material. In this review, we summarized the design of functional xeno nucleic acids and their applications in the biomedical field.     

Single-Crystal X-Ray Diffraction Studies of Oligonucleotides and Oligonucleotide–Drug Complexes

Nucleic acids constitute the library of genetic information for all living organisms. They also play a regulatory role in many biological events concerned with the utilization of genetic information. The double-helical model of DNA, proposed by Watson and Crick in 1953, suggested the structural basis for its biological role, but this insight into nucleic acid structures seems to have generated as many questions as it has provided answers. Experimental studies, in particular fiber diffraction work, yielded a wealth of information on the conformational flexibility of nucleic acids and on the importance of interactions with water and cations. Major advances in synthetic organic chemistry, with implications for molecular biology, propelled nucleic acid research forward in the late 1970s. The availability of milligram quantities of synthetic oligonucleotides of defined sequence and high purity paved the way for detailed and accurate structural analysis using single-crystal X-ray diffraction methods and, in more recent times, NMR spectroscopy. This article is a detailed survey of the structural results generated by crystallographic techniques as applied to DNA, RNA, and nucleic acid–drug complexes over the period 1979–1990. The appendix lists important definitions used in the characterization of oligonucleotide structures.     

Lipophilic nucleic acids — A flexible construction kit for organization and functionalization of surfaces

Lipophilic nucleic acids have become a versatile tool for structuring and functionalization of lipid bilayers and biological membranes as well as cargo vehicles to transport and deliver bioactive compounds, like interference RNA, into cells by taking advantage of reversible hybridization with complementary strands. This contribution reviews the different types of conjugates of lipophilic nucleic acids, and their physicochemical and self-assembly properties. Strategies for choosing a nucleic acid, lipophilic modification, and linker are discussed. Interaction with lipid membranes and its stability, dynamic structure and assembly of lipophilic nucleic acids upon embedding into biological membranes are specific points of the review. A large diversity of conjugates including lipophilic peptide nucleic acid and siRNA provides tailored solutions for specific applications in bio- and nanotechnology as well as in cell biology and medicine, as illustrated through some selected examples.     

Phototriggers for nucleobases with improved photochemical properties

Synthesis and photochemical properties of new photoremovable protecting groups for nucleobases are described. Four caged 2'-deoxycytidines (dCs) were synthesized, and their photochemical properties were measured under simulated physiological conditions. Two new coumarin-caged dCs show better photochemical and photophysical properties than those of the caged dCs having previously reported caging groups.     

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.     

离子液与蛋白质和核酸相互作用的研究

离子液因其具有良好的生物兼容性和独特的理化性质,近年来在生物催化和生物大分子蛋白质与核酸的分离分析领域得到广泛应用。离子液与生物大分子相互作用的研究是离子液相关理论与应用研究的基础,有关离子液与蛋白质和核酸相互作用的机理研究受到关注。本文简要介绍了常用离子液的分类,离子液与蛋白质分子作用的机理,离子液与核酸分子作用的机理,以及离子液在酶催化反应、生物分子分离、生物分子电化学分析和毛细管电泳分析中的应用,并主要综述了近年的相关研究和应用进展。