Neomycin binding

TABLE 11.1. Association Constants of Various Nucleic Acids with Neomycin. From top to bottom, various polynucleotides with their conformational preference (B- to A-form) are listed in 10 mM sodium cacodylate, 100 mM NaCl, 0.1 mM EDTA, pH 6.8. RNA targets that have previously been shown to bind neomycin are also listed. These targets are examples of RNA secondary structures that show high-affinity binding to aminoglycosides. Solution conditions for RNA targets vary as shown... 

A more recently discovered ribozyme that binds neomycin, RNase P is responsible for the maturation at the 5 end of all tRNA in both prokaryotes and eukaryotes. Bacterial RNase P consists of a small RNA and protein subunit, of which the RNA acts as the catalyst in the cleavage reaction. Like the group 1 intron ribozyme, inhibition of activity by such aminoglycosides as neomycin is suggested to occur as a result of the displacement of two important Mg ... 

Wayman et al studied the binding of neomycin to the filtration materials celite, cellulose powder and Seitz filters. Neomycin was found to be adsorbed on all three materials. Acid-washing the cellulose powder failed to desorb all of the neomycin. 

A number of workers have utilised electrophoresis to establish the formation of a complex between neomycin and the proteins in blood-serum and plasma- - -, 105,106,107,108,109,110,111. However, the nature of the complex is still unknown. Geitman has extensively studied the phenomena of protein-binding of antibiotics- -- -- - > 112. ... 

Geitman reported that neomycin did not bind to any of the protein fractions when added to serum but bound to the isolated albumin and globulin fractions. An earlier paper H described the globulin-neomycin complex to be of greater stabil-... 

Recently, two research groups have independently synthesized the conforma-tionally constrained neomycin derivatives, 74, with the 2 -NH2 group linked to the C-5" (Scheme 4.13). The information from X-ray crystallography has revealed a drastic conformational flipping of the 2-deoxystreptamine component between the binding sites of rRNA and ANT(40. ° Thus, it is proposed that an intramolecular link may obstruct the needed conformational change for ANT(4 )-catalyzed modification. Compound 74 shows lower activity against... 

Dimers of kanamycin and neomycin have also been synthesized (Figure 4.14). The 5"-OH and 6 -OH are the only primary hydroxy groups on neomycin and kanamycin, respectively, and often served as the point of modification. The studies in these articles, however, focus on the binding affinities of these kanamycin and neomycin dimers toward various RNA sequences of biological interest. 

The structures of tobramycin and neomycin B in complex with aptamer RNAs also display the importance of interactions between the amino groups of aminoglycosides and the phosphate backbone of RNA. In the neomycin-aptamer complex, the 6 -amino group on ring I interacts with the phosphate backbone. Paromomycin, in which the 6 position of ring I is a hydroxyl group, binds... 

Uniquely, the Cu +-neomycin B system has been shown to form two-centered copper complexes at pH values below 6.5 if the metal ion is present in excess (Table 8.3) with less than 15% (relative to total Cu + present) of mononuclear species detected at pH values in the range of 4 to 6. At a 2 1 Cu + neomycin B stoichiometric ratio it was shown that only the dinuclear species exists in solution at pH 7.5. The second binding site in the dinuclear complex was proposed to be in ring D, however, this unique feature is only observed in the case of the copper complex of neomycin B. 

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