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 w ith 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 compar ed with those of the corresponding unmodified antibiotics and their N- 15-acetyl derivatives. The most active derivatives were the octapeptid es with N-terminal glycine or lysine whose in vitro activity was compa rable to that of the parent teicoplanins. The glycinyl and lysyl deriv atives of CTA/2 showed better activity than CTA/2 against clinical iso lates of Staphylococcus epidermidis and S. haemolyticus for which teic oplanin MICs were relatively high. No significant difference in their antibacterial activity was observed between octapeptides containing L- or D-lysine.