Aminoglycoside acetyl transferases AACs

The synthetic methods for chemoselective N-acylation of AGs discussed previously in this chapter offer access to a variety of semisynthetic AG analogs however, the diversity of AG structures makes it challenging to chemoselectively modify each of the multiple amine positions on the various AGs using the existing synthetic methodologies [87-91]. An additional approach to overcome this problem exploits the chemoselectivity of aminoglycoside acetyl transferases (AACs) for the in vitro chemoenzymatic generation of novel chemoselectively N-acylated... 

A newly Isolated, plasmid-determined acetyl transferase [AAC(3)-III] inactivates most aminoglycosides, including gentamicin and apramycln, but not butirosin, amikacin or fortlmlcin. Earlier data had indicated no cross-resistance of apramycln with other aminoglycosides. " A broad-... 

Bacterial resistance to aminoglycoside antibiotics in the clinic is most commonly the result of bacterial elaboration of R factor-mediated enzymes that N-acetylate (aminoglycoside acetylase [AAC]), 0-phosphorylate (aminoglycoside phosphorylase [APH]), and 0-adenylate (aminoglycoside nucleotide transferase [ANT]) specific functional groups, preventing subsequent ribosomal binding (Fig. 38.26). In some... 

Auclair et al ° have demonstrated the first synthesis of a phosphonate-linked aminoglycoside-coenzyme A derivative (515), which was a superior mimic of the tetrahedral intermediate proposed for catalysis by AAC(6 )s (aminoglycoside A-6 -acetyl-transferases) (Scheme 134). 

---