Ribosomal peptidyl transferase: Recognition points on the 3′-terminus of AA tRNA

Current models of the active center of ribosomal peptidyl transferase generally invoke a P-subsite which binds the CCA terminus of peptidyl-tRNA and an Asubsite which binds at least part of the CCA terminus of AA-tRNA [I] . Since the CCA sequence occurs at the 3’-terminus of all tRNAs, it is at least indirectly involved in peptide bond formation. It therefore follows that the elucidation of the role of these sequence in binding to peptidyl transferase sites is a necessary step toward understanding the nature of the peptide bond formation center. One approach which has met with some success in investigating the involvement of the CCA termini of peptidyland AA-tRNAs in the peptidyl transferase reaction has involved the use of N-acylaminoacyl or aminoacyl terminal fragments of tRNA as substrate analogs of the parent molecules [2-l 61. Compounds of this type (e.g., AA-oligonucleotides or AA-nucleosides) can be prepared by chemical synthesis or by enzymatic degradation of the corresponding tRNA derivatives. Despite its complexity, chemical synthesis of substrate analogs for peptidyl transferase offers the important advantage that unnatural compounds, i.e., nonCCA-AA sequences, can be synthesized. The study of such compounds in ribosomal systems can thus enable