The ribosome is the biological machine that has evolved to generate encoded polymers. The development of a novel in vitro selection procedure for evolving the ribosome to recognize and perform chemistry on altered substrates is described. Specifically, the in vitro selection system allows for the isolation of 23S rRNA derivatives that are functionally enriched for catalysis on altered substrates. Redirection of the ribosomes ? substrate specificities will allow for the generation of encoded, non-peptidyl products that will have application to combinatorial chemistry. Herein is described the application of this technology to the incorporation by the ribosome of altered substrates including phosphate substitutions for the aminoacyl ester linkage to the tRNA, beta-amino acids and N-derivatized amino acids. This technology should allow for the generation of combinatorial chemical libraries that can be readily screened and deconvoluted to identify novel, biologically stable compounds.
Type of Offer:
« More Tools Patents