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.
D000217:Acyltransferases / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D010458:Peptidyl Transferases / Q000378:metabolism*; D011691:Puromycin / Q000378:metabolism*; D012270:Ribosomes / Q000201:enzymology / Q000378:metabolism*; D013033:Sparsomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D011691:Puromycin; D013033:Sparsomycin; D000217:Acyltransferases; D010458:Peptidyl Transferases