Surface-promoted replication and exponential amplification of DNA analogues
Surface-promoted replication and exponential amplification of DNA analogues
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DOI：
10.1038/24343
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发表时间：
1998-11-19
期刊：
影响因子：
64.8
通讯作者：
von Kiedrowski, G
中科院分区：
文献类型：
--
作者：
Luther, A;Brandsch, R;von Kiedrowski, G
自我复制化学系统已被设计和研究，以确定分子复制的最低要求（1），将原理转化为合成超分子系统（2），并更好地理解自组织过程的范围和局限性（3），被认为与地球上生命的起源有关（4）。目前的实施方式利用寡核苷酸类似物（5-12）、肽（13-17）和其他分子（18-24）作为模板，并且基于用于模板形成的自催化、交叉催化或共同催化途径。这些系统的一个共同问题是产物抑制，导致抛物线而不是指数放大（25）。在达尔文的意义上，较胖的人是自然选择的动态前提（26，27）。我们在这里描述了一个迭代的，逐步的化学复制程序，允许寡核苷酸类似物的浓度呈指数级增加。该过程使用固体支持物的表面，称为SPREAD（DNA类似物的表面促进复制和指数扩增）。通过化学连接在固定化模板上，从前体片段合成拷贝，然后释放和固定化以成为新的模板。迭代地重复该过程。支持物的作用是分离互补模板，其将在溶液中形成稳定的双链体。SPREAD结合了固相化学和化学复制的优点，可进一步开发用于RNA、肽和其他模板的非酶和酶扩增，以及人工化学系统中的体外进化和竞争研究。类似的过程也可能在地球生命的起源中发挥了作用，因为最早的复制系统可能通过在矿物表面传播而增殖。
Self-replicating chemical systems have been designed and studied to identify the minimal requirements for molecular replication(1), to translate the principle into synthetic supramolecular systems(2) and to derive a better understanding of the scope and limitations of self-organization processes(3) that are believed to be relevant to the origin of life on Earth(4). Current implementations make use of oligonucleotide analogues(5-12), peptides(13-17), and other molecules(18-24) as templates and are based either on autocatalytic, cross-catalytic, or collectively catalytic pathways for template formation. A common problem of these systems is product inhibition, leading to parabolic instead of exponential amplification(25). The fatter is the dynamic prerequisite for selection in the darwinian sense(26,27). We here describe an iterative, stepwise procedure for chemical replication which permits an exponential increase in the concentration of oligonucleotide analogues. The procedure employs the surface of a solid support and is called SPREAD (surface-promoted replication and exponential amplification of DNA analogues). Copies are synthesized from precursor fragments by chemical ligation on immobilized templates, and then Liberated and immobilized to become new templates. The process is repeated iteratively. The role of the support is to separate complementary templates which would form stable duplexes in solution. SPREAD combines the advantages of solid-phase chemistry with chemical replication, and can be further developed for the non-enzymatic and enzymatic amplification of RNA, peptides and other templates as well as for studies of in vitro evolution and competition in artificial chemical systems. Similar processes may also have played a role in the origin of life on Earth, because the earliest replication systems may have proliferated by spreading on mineral surfaces(28-33).