Aminoglycosides interaction

Kirsebom LA, Virtanen A, Mikkelsen NE. Aminoglycoside interactions with RNAs and nucleases. Handb Exp Pharmacol. 2006 173 73-96. 

C.-H. Wong and F.-S. Liang, Surface plasmon resonance study of RNA-aminoglycoside interactions, Methods Enzymol, 362 (2003) 340-353. 

H. Wang and Y. Tor, RNA-aminoglycoside interactions design, synthesis, and binding of amino-aminoglycosides to RNA, Angew. Chem. Int. Ed. Engl, il (1998) 109-111. 

The nature of the actual interaction cannot be established from con-ductimetry alone. In a discussion of the reaction between heparin and poly cations, Rembaum and Haack noted the associated liberation of sodium chloride, and inferred that changes in chain conformations must occur during the reaction. They suggest that the mechanism of the reaction involves an isoelectric jump, on which there has been a considerable amount of experimental and theoretical work, in order to elucidate the reaction thermodynamics. A similar mechanism may well be operative in the heparin-aminoglycoside interactions. 

The preferred substrates of acetyltransferases are amino-groups of antibiotics, like chloramphenicol, strepto-gramin derivatives, and the various aminoglycosides. The modification is believed to block a functional group involved in the drug-target-interaction. All acetyltransferases use acetyl-coenzyme A as cofactor. 

Discuss the uses, general drug action, contraindications, precautions, interactions, and adverse reactions of the fluoroquinolones and aminoglycosides. 

Arya DP (2005) Aminoglycoside-Nucleic Acid Interactions The Case for Neomycin. 253 ... 

Similar well-shaped responses have been obtained at a gold electrode using the aminoglycoside neomycin (neomycin sulfate), which is a positively charged promoter favouring the electrostatic interaction with negatively charged proteins.36... 

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... 

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). 

Recently, Tor and co-workers have analysed the interaction between the cyclic analog 2 and the corresponding paromomycin derivative with the A-site sequence and also with the HIV TAR RNA fragment [47]. At pH 7.5, the decrease in affinity for the locked derivatives with respect to the parent aminoglycosides is 22-14 fold for the A-site and 11-2 fold for the HIV TAR sequence. The differences with respect to the natural ligands are significantly reduced at acid pH. 

E., Hofstadler, S. A., Griffey, R. H. Synthesis of neomycin analogs to investigate aminoglycoside—RNA interactions. Synlett 2003, 9,... 

Figure 3.1A. Interaction of aminoglycosides with the acceptor site of the 30S ribosome. Schematic representation of (A) paromomycin and (B) streptomycin interactions with the 16S rRNA and ribosomal protein SI2.

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