Neamine dimers

By employing a 27-nucleotide RNA that represents the binding site of aminoglycoside toward the 16S rRNA, it has been found that neamine binds to such an rRNA sequence in a 2 1 ratio. Several neamine dimers were then constructed to investigate their antibacterial activity and their capability to resist or inhibit the action of AME (Scheme 4.25). These neamine dimers displayed modest to excellent antibacterial activity (Table 4.16). In addition, these dimers have also been noted for their inhibitory effect against AAC(6 )-APH(2"). 

Scheme 4.25. Synthesis of neamine dimers. TABLE 4.16. MIC of Neamine Dimers...

Protected neamine dimers were prepared using a Quest 210 parallel synthesizer. 5-Ethylcarboxyl-1,3,2, 6 -tetraazido-6,3, 4 -tri-6>-benzylneamine (0.0826 mmol/tube was dissolved in 1.5ml/tube containing CH2C12 distributed to each tube, which was then treated with MP-carbodiimide resin (1.15mmol/g) followed by 1,12-dodecylamine (0.0413 mmol/tube). Solutions were agitated 16 hours, filtered, concentrated, and dimers isolated as colorless foams. 

Table 1 Selected experimental neamine dimers prepared using the Quest 210 parallel synthesizer and their corresponding mass spectra characterization...

The neamine dimers also displayed enhanced binding to a model A-site, and showed that neamine binds in a 2 1 fashion to the RNA A-site. The application of such novel compounds is certainly substantiated by characteristic activity... 

Fig. 11. Various neamine dimers and their respective activities with aminoglycoside deactivating enzymes. The numbers for each strain represent minimum inhibitory concentrations. Reprinted with permission. Copyright 2004 Wiley-VCH Verlag GmbH Co. KgaA.

Upon further screening and modification, two neamine/nebramine dimers were synthesized and assayed (Figure 4.13). A much improved activity was observed even against various clinically isolated strains of P. aeruginosa (Table 4.17). 

Conversely, Wong and co-workers took to snrveying the major groove through dimerization of neamine with either a polyglycol or polymethylene linker. The... 

Preparation of 5-ethylcarboxyl-l, 3,2, 6 -tetraazido-6,3,4 -tri-0-benzyl-neamine diamine dimer... 

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