RNA-PEPTIDE FUSIONS FOR THE IN-VITRO SELECTION OF PEPTIDES AND PROTEINS

Covalent fusions between an mRNA and the peptide or protein that it en codes can be generated by in vitro translation of synthetic mRNAs that carry puromycin, a peptidyl acceptor antibiotic, at their 3' end. The stable linkage between the informational (nucleic acid) and functiona l (peptide) domains of the resulting joint molecules allows a specific mRNA to be enriched from a complex mixture of mRNAs based on the prop erties of its encoded peptide. Fusions between a synthetic mRNA and it s encoded myc epitope peptide have been enriched from a pool of random sequence mRNA-peptide fusions by immunoprecipitation. Covalent RNA-pe ptide fusions should provide an additional route to the in vitro selec tion and directed evolution of proteins.