Abstract
Chemically modified RNA nucleotides have been introduced in the past into various ribozymes in order to understand RNA folding and the mechanism of RNA catalysis. Recently the ribosome, the largest natural ribozyme known to date, has been added to the list of enzymes amenable to synthetic biology. The chemically engineered ribosomes were active in various functional assays including single-turnover peptidyl transfer reaction as well as in vitro translation assays. Solid-phase synthesis of several non-natural nucleotide analogs and their subsequent introduction into the catalytic center of the ribosome, revealed the ribose 2-OH at position A2451 of 23S ribosomal RNA as key functional group for amide bond synthesis. By altering the chemical characteristics of the ribose at A2451 by replacing its 2-OH with selected functional groups demonstrated that hydrogen donor capability is essential for efficient transpeptidation. These findings in combination with data that accumulated over the past years allowed to propose a comprehensive model for peptide bond synthesis in which the A2451 2-OH directly assists in positioning one of the tRNA substrates via hydrogen-bond formation and thus supports amide bond synthesis via a proton shuttle mechanism. It is conceivable that cell-free translation systems employing rationally designed chemically engineered ribosomes can be established in the near future to produce peptides and proteins harboring unnatural amino acids.
Call for Papers in Thematic Issues
Catalytic C-H bond activation as a tool for functionalization of heterocycles
The major topic is the functionalization of heterocycles through catalyzed C-H bond activation. The strategies based on C-H activation not only provide straightforward formation of C-C or C-X bonds but, more importantly, allow for the avoidance of pre-functionalization of one or two of the cross-coupling partners. The beneficial impact of ...read more
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