Showing papers on "Ribostamycin published in 2002"
TL;DR: The results reveal the impact of specific alterations in aminoglycoside structure on the thermodynamics of binding to an A-site model RNA oligonucleotide and the salt dependencies of the RNA binding affinities of neomycin and paromomycin are consistent with at least three drug NH(3)(+) groups participating in electrostatic interactions with the host RNA.
Abstract: We use spectroscopic and calorimetric techniques to characterize the binding of the aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin to a RNA oligonucleotide that models the A-site of Escherichia coli 16S rRNA. Our results reveal the following significant features: (i) Aminoglycoside binding enhances the thermal stability of the A-site RNA duplex, with the extent of this thermal enhancement decreasing with increasing pH and/or Na+ concentration. (ii) The RNA binding enthalpies of the aminoglycosides become more exothermic (favorable) with increasing pH, an observation consistent with binding-linked protonation of one or more drug amino groups. (iii) Isothermal titration calorimetry (ITC) studies conducted as a function of buffer reveal that aminoglycoside binding to the host RNA is linked to the uptake of protons, with the number of linked protons being dependent on pH. Specifically, increasing the pH results in a corresponding increase in the number of linked protons. (iv) ITC studies ...
139 citations
TL;DR: A structural analysis of the crystal structure of the AAC(2′)-Ic from Mycobacterium tuberculosis suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.
Abstract: AAC(2')-Ic catalyzes the coenzyme A (CoA)-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides. The crystal structure of the AAC(2')-Ic from Mycobacterium tuberculosis has been determined in the apo enzyme form and in ternary complexes with CoA and either tobramycin, kanamycin A or ribostamycin, representing the first structures of an aminoglycoside acetyltransferase bound to a drug. The overall fold of AAC(2')-Ic places it in the GCN5-related N-acetyltransferase (GNAT) superfamily. Although the physiological function of AAC(2')-Ic is uncertain, a structural analysis of these high-affinity aminoglycoside complexes suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.
128 citations
TL;DR: Here, polar contacts between non-vicinal sugar units lead to an enhanced flexibility of the ribose glycosidic torsion phi, demonstrating unambiguously that both common beliefs are not to be generalized.
Abstract: 13 paginas, 14 figuras, 2 tablas.-- Supporting information for this article (Figures showing details of the
NMR analysis n and ribostamycin) is available on the WWW under
http://www.chemeurj.org or from the author.
22 citations
28 Aug 2002
5 citations
TL;DR: In this article, a laser spray interface for use in liquid chromatography/mass spectrometry (LC/MS) has been investigated with respect to the degradation of a thermally labile compound, ribostamycin.
Abstract: A laser spray interface for use in liquid chromatography/mass spectrometry (LC/MS) has been investigated with respect to the degradation of a thermally labile compound, ribostamycin. It was confirmed that few fragment ions were formed when the laser beam was focused to the center of the stainless steel capillary. When the laser beam was slightly off-centered, the sample ions suffered from the thermal degradation by the heated wall of the stainless steel capillary. A feasible observation of fragment ions for the thermally labile compounds by the wall heating would be useful for the structural elucidation of the sample molecules.