Photocleavage of Nucleic Acids.

Photocleavage of Nucleic Acids.
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DOI:
10.1002/chin.199830319
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发表时间:
1998-03
期刊:
影响因子:
62.1
通讯作者:
B. Armitage
B. Armitage
中科院分区:
化学1区
文献类型:
--
作者:
B. Armitage

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近年来,分子生物学的爆炸性增长为来自许多不同学科的科学家打开了大门。他们沿着这条道路,运用各自领域的工具和知识,解决具有基本和应用生物学重要性的问题。化学家做出重大贡献的领域之一是设计和开发用作结构探针和治疗剂的核酸切割剂。虽然天然酶在许多应用中非常有用,但它们的大尺寸和/或有限的序列识别能力范围阻止了它们的普遍使用。例如,在重组DNA合成中至关重要的限制性内切酶,只能在特定的4-8个碱基对(bp)序列处切割DNA,这些序列通常是回文的(即,两条链上的序列相同)。需要以更高水平的序列选择性(> 8bp)或在非回文序列处切割的应用需要具有扩展的序列识别特征的新切割剂。或者,RNA结构探测实验通常涉及用一系列核糖核酸酶部分消化RNA底物,所述核糖核酸酶的序列和二级结构偏好不同。开发新的RNA切割剂,切割任何单链区域,无论序列如何,可以大大简化这些实验。天然核酸切割剂的这些缺点为化学家引入合成切割剂提供了机会。1本文综述的主题是一类光化学活化的合成核酸切割剂。光裂解剂的一个吸引人的特性是,待研究的系统的所有组分可以混合在一起而不引发化学反应,直到样品被照射。控制光线的能力,
The explosive growth in molecular biology has opened doors through which scientists from many different disciplines have passed in recent years. Along the way they have applied the tools and knowledge of their respective fields to addressing questions of fundamental and applied biological importance. One of the areas in which chemists have made substantial contributions is in the design and development of nucleic acid cleavage agents for use as structural probes and therapeutic agents. While natural enzymes have been extremely useful in many applications, their large size and/or limited range of sequence-recognition capabilities prevent their general use. For example, restriction enzymes, which are so critical in the synthesis of recombinant DNA, will only cleave DNA at specific 4-8 base pair (bp) sequences that are usually palindromic (ie, the sequence is the same on both strands). An application which demands cleavage with a higher level of sequence selectivity (> 8 bp) or at nonpalindromic sequences requires a new cleavage agent with expanded sequence recognition features. Alternatively, RNA structure probing experiments typically involve partial digestion of the RNA substrate with a series of ribonuclease enzymes, which differ in their sequence and secondary structure preferences. Development of new RNA cleavage agents that cleave at any single-stranded region, regardless of sequence, could greatly simplify these experiments. These shortcomings of natural nucleic acid cleavage agents provide opportunities for chemists to introduce synthetic cleavers. 1The topic of this review is a class of synthetic nucleic acid cleavage agents that are activated photochemically. One appealing characteristic of photocleavage agents is the fact that all components of a system to be studied can be mixed together without initiating the chemical reaction until the sample is irradiated. The ability to control light, in both a