Synthesis and Evaluation of Novel Neamine-Nucleoside Conjugates as Potential Antibiotic Targets for Escherichia coli 16S Ribosomal RNA

Based on the nucleobase rich character of the binding pocket of A-site 16S ribosomal RNA of Escherichia coli, it was proposed that the neamine moiety of synthesized Neamine-nucleoside conjugates could bind to the groove of RNA while the nucleobase moiety would bind specifically to the sequence of th...

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Published inMethods in molecular biology (Clifton, N.J.) Vol. 1870; p. 151
Main Authors Yang, Zhen-Jun, Concilio, Maria-Grazia, Ramesh, Vasudevan, Zhang, Li-He
Format Journal Article
LanguageEnglish
Published United States 2019
Subjects
Neamine nucleoside conjugate
16S rRNA
Aminoglycosides
NMR spectroscopy
Antibiotic resistance
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Summary:Based on the nucleobase rich character of the binding pocket of A-site 16S ribosomal RNA of Escherichia coli, it was proposed that the neamine moiety of synthesized Neamine-nucleoside conjugates could bind to the groove of RNA while the nucleobase moiety would bind specifically to the sequence of the 16S rRNA A-site fragment. Thus the designed conjugate compound 5 was found to have the same dissociation constant as neamine for binding to 16S rRNA and the neamine-amino acid substituted nucleoside conjugate 8 and 9 showed 6.3 and 4.8 times greater RNA binding affinity, respectively, as compared with neamine. The results obtained successfully demonstrate the need for chemically modifying neamine and probe the changes induced using NMR protocols to assist in the discovery of new aminoglycoside antibiotics.
ISSN:1940-6029
DOI:10.1007/978-1-4939-8808-2_11