Synthesis and biological activity of photoactive derivatives of erythromycin.
Five photoactive derivatives of erythromycin have been synthesized by linking to 9(S)-aminoerythromycin either an aryl azide or a p-nitrophenyl ether. One derivative is an amide formed by reaction with (5-azido-2-formyl-phenoxy)acetic acid. Three derivatives are also amides, synthesized with 4-(p-nitroguaiacoxy)butanoic acid as a photoreactive group either directly or by interposing an amino acid (glycine or tyrosine). The last derivative is the product of the aldehyde condensation of aminoerythromycin with 10-(p-nitroguaiacoxy)decanal. Two of these derivatives can easily be made radioactive for affinity labeling studies either by reduction with [3H]borohydride (aryl azide derivative) or by 125I iodination (4-(p-nitroguaiacoxy)tyrosyl derivative). Although affected to different extents, the five erythromycin derivatives are biologically active and bind to the erythromycin-specific site on the bacterial ribosomes. In addition, the introduction of these groups changes the erythromycin inhibition pattern of peptide bond model reactions.
Arévalo
M A
MA
Centro de Biología Molecular, CSIC, Madrid, Spain.
Tejedor
F
F
Polo
F
F
Ballesta
J P
JP
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000254:growth & development; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004917:Erythromycin / Q000031:analogs & derivatives*; D004926:Escherichia coli / Q000254:growth & development; D008956:Models, Chemical; D010455:Peptides / Q000378:metabolism; D010777:Photochemistry; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010455:Peptides; D004917:Erythromycin