Effect of Sparsomycin Analogues on the Puromycin-Peptidyl Transferase Reaction on Ribosomes

Sparsomycin analogues in which the unique-S(O)CH2SCH3 moiety was replaced by a variety of more easily accessible side chains were evaluated as inhibitors of the peptidyl transferase reaction with bacterial ribosomes. Competitive inhibition of acetyl [14C]phenylalanylpuromycin formation revealed that the sulfur-containing side chain of sparsomycin could be replaced with hydrophobic moieties, whereas complete removal of the-S(O)CH2SCH3 side chain eliminated the ribosomal binding affinity of sparsomycin. The specificity for the D isomer of S-deoxo-S-propylsparsomycin has established that the chiral carbon of sparsomycin analogues must be identical with the chirality of D-cysteinol for ribosomal binding.