Binding aminoglycoside

Wong and coworkers in a recent investigation [163] studied the A-site-binding aminoglycosides, including the 4,5-disubstituted 2-deoxystreptamine derivatives (neomycin B, paromomycin, and ribostamycin) and the 4,6-disubstituted 2-deoxystrep-... 

C. RNA Molecules That Specifically Bind Aminoglycoside Antibiotics with High Affinities... 

Although the two subclasses of the A-site binding aminoglycosides are chemically distinct, they do share rings I and II in common and up to that point bind SOS in identical ways (60). Therefore, discussion of ring I and ring II modifications of both subclasses will be treated at the same time, without regard for whether or not a particular modification was observed in the 4,5 subclass or the 4,6 subclass (Fig. 6.4a). 

Fig. 18. Secondary structure of a construct of the TAR element of HIV-l found to bind aminoglycosides.

Treatment with aminoglycosides (gentamicin, tobramycin, and amikacin) can cause non-oliguric intrinsic ARF. Injury is due to the binding of aminoglycosides to proximal tubular... 

Also on the nucleic acid field, it has been shown95 that the distribution pattern of NH2/NH3 + /OH groups in natural aminoglycosides could indirectly influence their RNA binding properties and therefore their antibiotic functions. Indeed, the number and location of these polar groups is essential to modulate the conformation and dynamics of the glycoside with the concomitant implication for the RNA recognition process. 

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

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... 

Fig. 7 Schematic representation of the conformational differences (highlighted with a dotted box) exhibited by aminoglycosides in the binding pockets of RNA (a) and some of the enzymes involved in bacterial resistance (b). The glucose, 2-deoxy-streptamine and ribose units are numbered as I, II and III respectively...

Fig. 11 a Some representative binding curves obtained for derivatives 1 (black), 2 and 3 under identical conditions, b Schematic representation of the AG values measmed for the binding of aminoglycosides 1, 2, 3, 5 and 6 to the A-site... 

We have shown that the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. This feature allows the adaptation of these ligands to the spatial and electronic requirements of the different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the enzymes involved in bacterial resistance is consistent with this view. 

RNA, (ii) the screening for antiviral compounds that do not bind to RNA but bind specifically to target RNA polymerases, (hi) the evaluation of the binding of aminoglycosides to RNA, and (iv) the evaluation of the binding of DNA intercalators and minor groove binders to RNA. 

Crooke, S. T. Determinants of aminoglycoside-binding specificity for rRNA by using mass spectrometry. 

S. A. Determinants of aminoglycoside binding specificity to RNA subdomains. Ahstr Pap Am Chem Soc 2001, 221, CARB-007. 

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