The chiral synthesis and biochemical properties of electron rich phenolic sulfoxide analogs of sparsomycin.
A novel route to activated phenolic sulfoxide analogs of sparsomycin has been developed. These analogs display an enhanced "preincubation effect" as inhibitors of peptide-bond formation. This time-dependent component of inhibition, which is postulated to result from an enzyme-mediated Pummerer rearrangement, is the dominant route to inhibition in these activated analogs.
Flynn
G A
GA
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Ash
R J
RJ
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D003196:Computer Graphics; D004926:Escherichia coli; D066298:In Vitro Techniques; D008958:Models, Molecular; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D011691:Puromycin / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects; D013033:Sparsomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D011691:Puromycin; D013033:Sparsomycin; C062663:MDL 20828; D000217:Acyltransferases; D010458:Peptidyl Transferases