Aminoglycoside antibiotics design

TABLE 2.1. Aminoglycoside Antibiotics (AGAs), Designations, and Abbreviations Used Throughout This Chapter... 

Greenberg, W.C. et al.. Design and synthesis of new aminoglycoside antibiotics containing neamine as an optimal core structure correlation of antibiotic activity with in vitro inhibition of translation, J. Am. Chem. Soc., 121, 6527, 1999. 

Neomycin is a readily ionisable molecule and should thus be separable from other antibiotics by application of an electric field (zone electrophoresis). Various workers have successfully applied this technique to neomycin and Table 10 summarises the conditions reported in the literature. A number of authors described the qualitative separation of neomycin from other chemical-types of antibiotics using paper-electro-phoresis181,185,187 while Ochabl89 described systems specifically designed to separate compounds within the aminoglycoside group of antibiotics. 

The different 3D-shapes adopted by aminoglycosides in the RNA- and enzyme-bound states suggest a possible structure-based chemical strategy to obtain antibiotics with better activity against resistant bacteria. Assiun-ing that, in these cases, some degree of conformational distortion of the substrates is required for enzymatic activity, it should be possible to design a conformationally locked oHgosaccharide that still retains antibiotic activity, but that is not susceptible to enzymatic inactivation (Fig. 8) [41]. 

These selected studies demonstrate that carefully designed aminoglycosides can maintain antibiotic activity despite the presence of resistance elements that would inactivate compounds in current clinical use. 

Design of aminoglycoside to function as the inhibitor (or inactivator) of AME has been reported less frequently than those involved in the modification of aminoglycosides to be used directly as antibiotic. However, these studies may provide... 

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