Aminoglycosides structures

Structure-Activity Relationships Among Aminoglycoside Derivatives... 

E Wolf, A Vassilev, Y Makmo, A Sail, Y Nakatam, SK Burley. Crystal structure of a GCN5-related N-acetyltransferase Serratia marcescens aminoglycoside 3-N-acetyltransferase. Cell 94 51-61, 1998. 

The aminoglycosides are potentially neurotoxic, nephrotoxic, and ototoxic and are capable of causing permanent damage to tiiese organs and structures. The nurse notifies the primary health care provider immediately when one or more signs and symptoms of tiiese adverse reactions is suspected. 

Reden, J., and Diirckheimer, W. Aminoglycoside Antibiotics — Chemistry, Biochemistry, Structure-Activity Relationships. 83, 105-170 (1979). 

In addition to terpenes (as described above), carbohydrates have also been used as substrates in domino metathesis reactions, the aim being to synthesize enan-tiopure polyhydroxylated carbocyclic rings. These structures are components of several biologically active compounds such as aminoglycoside antibiotics [254], inositol phosphates [255], and carbanucleosides [256]. An efficient entry to this skeleton was developed by Madsen s group using a domino RCM/CM of the carbohy-... 

Wright GD, Berghuis AM, Mobashery S Aminoglycoside antibiotics. Structures, functions, and resistance. Adv Exp Med Biol 1998,456 27-69. 

The three-dimensional structure of the aminoglycosides plays an essential role in their interaction with both RNA and the enzymes involved in the antibiotic inactivation and thus determines their biological function. A proper understanding of the different factors that govern aminoglycoside-RNA/protein interactions requires a detailed knowledge of the three-dimensional structure, and conformational properties of these oligosaccharides in both the... 

Structure and Flexibility of Aminoglycoside Antibiotics Bound to the A-site RNA... 

The 3D structures of several aminoglycoside-enzyme complexes have been described recently by X-ray methods [35,36]. Interestingly, in some cases, the 3D structure of the antibiotic in the enzyme binding site significantly... 

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]. 

The design of our conformationally constrained aminoglycosides is based on the structural information available for the RNA-paromomycin complex [21-26]. It is known that positions 05m and N2i are hydrogen bonded within the ribosome bound state. Thus, in our analogs, this interaction has been replaced by either a direct covalent bond, as in 2, a two-methylene bridge, as in 3, or by a salt bridge, as in 4 (see Fig. 9). 

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