Template ligation

The central component of this RNA World scenario is a replication system that can make copies of the genetic material to grow and produce progeny. The most basic scenario is a simple templated ligation of small oligomers in a cyclical replication scheme (13-16), but ultimately a catalytic entity responsible for this crucial function of replication would be necessary. The simplest example is a single self-replicating ribozyme that can copy itself. More elaborate scenarios for... 

Brandis, J. Bolchakova, E. V. Karger, A. E. Detection of small RNAs based on RNA-templated ligation and PCR amplification. U.S. Pat. Appl. Publ. 

Fig. 4. Steps in making a cDNA library. Cellular mRNA is used as a template to make a complementary DNA. This cDNA is then ligated to a plasmid,...

Wu, D and Wallace, R. (1989). The ligation amplification reaction (LAR)—amplification of specific DNA sequences using sequential rounds of template dependent ligation. Genomics 4,560-569. 

Templating by oligopeptides is a more complicated proposition than the essentially linear solution available for nucleotide systems. Regular structures can be designed, but conformations typically depend on pH, and template aggregation is potentially more of a problem. Two groups have achieved success in the sort of template-mediated ligation reactions we have discussed for nucleotide systems, and their results illustrate the problems.160,611... 

The ligation product is a copy of the template, so this represents a self-replication procedure for Pl-Cys-P2. Initial rates depend on the square root of the template concentration (a common observation, readily explained where the template is active as the monomer but present mostly as the dimer), but rates fall off, as expected, as the product accumulates. 

Attaching cyclic, bidentate 1-hydroxy-177-pyridin-2-thione, 1-hydroxy-177-pyridin-2-one (1,2-HOPO) and 2-hydroxy-277-isoquinolin-l-one (1,2-HOIQO) ligating units via their C-6 carbon to TREN template produced 19 , 20 and 21 , respectively. 

Chirality can be introduced at two possible sites on the basic tripodal structures replacing the tripodal template by a chiral template or modifying each arm with a chiral component, usually as amino acids, between the template and the ligating groups. Incorporation of amino acids inevitably introduced an amide bond known to promote intricate H-bonding networks. The latter can be applied to the various templates described so far. 

Figure 4.4 OrgeFs template-directed oligomerization. The main process in template-directed oligomerization of mononucleotides acmally occurs at the dimer or trimer level. When an activated mononucleotide is allowed to react in the presence of a complementary polynucleotide template, dimers are first formed in a non-catalyzed phase of the reaction they then bind to the template and are ligated and extended. (Adapted from Schwarz, 1998.)...

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