Octapeptide derivatives of teicoplanin antibiotics.
A series of octapeptide derivatives of teicoplanin-A2 component 2 (CTA/2), its aglycone (TD), and the L-lysyl derivatives of an amide of CTA/2 and TD, were prepared by condensation of the terminal amino group with N-hydroxysuccinimidyl esters of tert-butyloxycarbonyl (BOC) L- and D-amino acids, followed by acidic (TFA) removal of the BOC protecting function. The antimicrobial properties of these compounds were compared with those of the corresponding unmodified antibiotics and their N15-acetyl derivatives. The most active derivatives were the octapeptides with N-terminal glycine or lysine whose in vitro activity was comparable to that of the parent teicoplanins. The glycinyl and lysyl derivatives of CTA/2 showed better activity than CTA/2 against clinical isolates of Staphylococcus epidermidis and S. haemolyticus for which teicoplanin MICs were relatively high. No significant difference in their antibacterial activity was observed between octapeptides containing L- or D-lysine.
Marion Merrell Dow Research Institute, Lepetit Research Center, Gerenzano (Varese), Italy.
A
A
Malbarba
R
R
Ciabatti
R
R
Scotti
B P
BP
Goldstein
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D017334:Teicoplanin