Self-replication template

A recent discovery that RNA will act as a self-catalyst, called a ribozyme, leads to a simple three-step model for self-replication - this might include a surface. In the model (Figure 8.18), the template molecule T is self-complementary and is able to act as an autocatalyst. In the first step, it reversibly binds with its constituents A and B, forming the termolecular complex M. The termolecular complex undergoes irreversible polymerisation and becomes the duplex molecule D. Reversible dissociation of D gives two template molecules T, which can initiate new replication. The model preserves the order of the moieties on the template (the direction of the arrow) and the backbone, which may be on the surface... 

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. 

Hydrogen-Bonding Templates in Self-Replicating Systems. 125... 

In the previous example the template is unrelated to the starting materials and to the final product. However, if the product formed by templation is the actual template, a self-replicating system emerges (see Scheme 42). 

These examples have demonstrated that it is possible to use the templating properties of a compound to accelerate its own formation. This is a potentially very attractive approach for the production of large quantities of a specific product with high selectivity. Furthermore, synthetic self-replicating systems also provide interesting models for their biological counterparts, which in turn could provide important clues to understand chemical evolution and indeed the origin of life itself. 

In spite of their attractive features, one of the problems usually encountered in self-replicating systems is the formation of very stable dimmers between the template and the complementary product formed. This obviously imposes important limitations to the use of self-replicating processes for the formation of large quantities of a specific product. 

The machinery of the amphiphilic polypeptide templates has been successfully used to engineer self-replicating peptides. The principles described above are... 

One limit to this beautiful chemistry hes in the requirement of selfcomplementarity of the self-replicating sequences. The more general case of a template working by complementarity was also investigated by von Kiedrowski s group (Sievers et al, 1994). As noted by Burmeister (1998), the underlying principle in this case is a cross-catalytic reaction in which one strand acts as a catalyst for the formation of the other strand. This is illustrated in Figure 7.6. 

Figure 7.7 Self-replication of ammidinium carboxylate templates. (Adapted from Burmeister, 1998.)...

Figure 7.8 General scheme of the SPREAD procedure of self-replication, (a) A template is immobilized by an irreversible reaction with the surface of a solid support, (b) The template binds complementary fragments from solution, (c) The fragments are linked together by chemical ligation, (d) The copy is released, and re-immobilized at another part of the solid support to become a template for the next cycle of steps. Irreversible immobilization of template molecules is thus a means to overcome product inhibition. (Adapted from Luther et al, 1998.)...

The original system is based on peptides that contain heptad repeats, where the first and fourth positions of the repeat are hydrophobic amino acids. Such sequences form a-helices, which assemble into coiled-coil structures, as represented in Figure 7.10. The principle is then the same as that used for von Kiedrowski s self-replicating nucleotides (von Kiedrowski 1986), in the sense that a full-length peptide template (having in this case 32-35 residues) directs the condensation of the two half-length peptide substrates. 

A first approach to a synthetic minimal cell the replication of a RNA template proceeded simultaneously with the self-replication of the vesicles. 

Lauceri, R., Raudino, A., Scolaro, L. M Mical, N., and Purrello, R. (2002). From achiral porphyrins to template-imprinted chiral aggregates and further self-replication of chiral memory from scratch. / Am. Chem. Soc., 124, 894-5. 

Self-replication takes place when a molecule catalyses its own formation by acting as template for the constituents, which react to generate a copy of the template. Such systems display autocatalysis and may be termed informational or non-infor-mational depending on whether or not replication involves the conservation of a sequence of information [9.196]. A problem is the occurrence of product inhibition when the dimer of the template, formed after the first condensation round, is too stable to be easily dissociated by the incoming components for a new cycle. 

In self-replicating systems employing three starting constituents competition between constituents can occur [9.205]. Such processes are on the way to systems displaying information transfer, whereas the two-components ones are non-infor-mational. A shift from parabolic kinetics to exponential growth of the template concentration is required for a selection process to take place [9.197]. The evidence for self-replication on the basis of template-directed autocatalysis as in 184 requires detailed mechanistic investigation on the origin of the catalytic effects observed [9.206]. 

Since the work of Kelly, there have been very few reports that focus upon applications of synthetic linear templates to chemical synthesis. Most recent studies have focused on systems that self-replicate [13]. A synthetic system based on a barbituric acid has been shown to organize two cinnamates in apolar media, by way of N-H N and N-H O forces, for a regiocontrolled [2 + 2] ultraviolet-(UV) induced cycloaddition reaction (Figure 3b) [16]. Similar to the system of Kelly, a mixture of products was attributed to free rotation about C-C bonds of the reactants. 

One cannot deny the fact that the origin of unlimited heredity is an unsolved problem. Perhaps compartmentation will help solve this problem as well, so that long templates could self-replicate within vesicles without enzymatic aid. 

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