BiomedExperts: A simple structural-based approach to prevent aminoglycoside inactivation by bacterial defense proteins. Conformational restriction provides effective protection against neomycin-B nucleotidylation by ANT4.

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2005: Asensio Juan Luis; Hidalgo Ana; Bastida Agatha; Torrado Mario; Corzana Francisco; Chiara Jose Luis; García-Junceda Eduardo; Cañada Javier; Jiménez-Barbero Jesús
A simple structural-based approach to prevent aminoglycoside inactivation by bacterial defense proteins. Conformational restriction provides effective protection against neomycin-B nucleotidylation by ANT4.
Journal of the American Chemical Society 2005;127(23):8278-9.

Herein, we describe how the conformational differences exhibited by aminoglycosides in the binding pockets of the ribosome and those enzymes involved in bacterial resistance can be exploited in the design of new antibiotic derivatives with improved activity in resistant strains. The simple modification shown in the figure, leading to the conformationally restricted 5, provides an effective protection against aminoglycoside inactivation by Staphylococcus aureus ANT4, both in vivo and in vitro.

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