Sulfoxide configuration in sparsomycin determines time-dependent and competitive inhibition of peptidyl transferase.
Sparsomycin, ScRs configuration, was the most potent of the four possible stereoisomers as a competitive inhibitor of peptide bond formation. In addition, the configuration of the two chiral centers dictated whether the compound exhibited time- and temperature-dependent inhibition of peptidyl transferase when incubated with polysomes prior to enzyme assay. The data corroborate the thesis that a peptidyl transferase-mediated acylation of the pivotal sulfoxide moiety and subsequent Pummerer rearrangement play a significant role in the inhibitory properties of sparsomycin.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D008968:Molecular Conformation; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D013033:Sparsomycin / Q000494:pharmacology*; D013237:Stereoisomerism; D013816:Thermodynamics
D000903:Antibiotics, Antineoplastic; D013033:Sparsomycin; D000217:Acyltransferases; D010458:Peptidyl Transferases