The Catalytic Spectrum of Artificial Ribozymes

In the following the scope of in vitro selected ribozymes will be described with special regard to organic chemistry. Several highlights will be discussed in detail. In Table 14.2 the variety of reactions catalysed by ribozymes is summarized. 

Although the RNA world presumably existed almost four billion years ago, X-ray-structures of the ribosome seem to exhibit fragments of this ancestral era. The structures revealed that RNA-mediated catalysis plays an important role in the peptide synthesis of the ribosome. The key step in translation is catalysed only by the ribonucleic acid component of the ribosome, without any direct contribution of proteins from the spatial vicinity. That impressively demonstrates the catalytic potential of RNA in a biochemical reaction that may arguably be called the most important ever. 

An artificial ribozyme mimics this translation step of the ribosome. The spedlity of this selected ribozyme is based on the recognition of an adenosine moiety of the amino acid ester and allows the utilization of leucine- and phenylalanine- as weU as methionine-derivatized substrates. This tolerance for various amino acids indicates the possibility of selecting more general ribozymes for protein synthesis. Furthermore, a related ribozyme efficiently catalyses the synthesis of -30 different dipeptides from an aminoacyl-adenylate substrate. Ribozyme-mediated synthesis of uncoded peptides might have been an important step in the transition from a RNA to a peptide world before the anergence of the ribosome.  

Another important development was the isolation of a ribozyme which performs nncle-otide synthesis by forming a glycosidic linkage from activated ribose (pRpp) in a way similar to the modem biosynthesis of nucleotides. 

Before the discovery of catalytic RNA, the principal indications of a possible RNA world had been the role of tRNA and ribosomal RNA in translation, the use of RNA as genetic material in retrovimses, and the ubiquitous occurrence of RNA-related enzymatic co-substrates like GTP, ATP, AMP, cAMP, SAM, FADH2 and NAD in all major metabolic pathways. Clearly, the capability of RNA to employ these and other nbiqnitous co-substrates in catalysis must be expected.  

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