Design of new photoaffinity labels for ribosomal peptidyltransferase.

The chemical syntheses of 6-azido-2'(3')-O-L-phenylalanylpurine ribonucleoside (4a), 2'(3')-O-(4-azido-L-phenylalanyl)adenosine (4b), and cytidylyl(3' leads to 5')-6-azido-2'(3')-O-L-phenylalanylpurine ribonucleoside (7) are described. 6-Azidopurine ribonucleoside 5'-triphosphate (10) was also synthesized starting from 6-methylmercaptopurine ribonucleoside. All of these compounds (4a, 4b, 7, and 10) are readily photolyzed by ultraviolet (UV) light. Compounds 4a, 4b, and 7 are active in the ribosomal peptidyltransferase-catalyzed release of the Ac-Phe residue from the Ac-Phe-tRNA-70S ribosome-poly(U) complex. It follows that the 6-azidopurine moiety of compounds 4a and 7, as well as the 4-azido-L-phenylalanine moiety of 4b, are recognized by the peptidyltransferase enzyme, and therefore these moieties are suggested for incorporation into tRNA as photoaffinity labeling reagents.