2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin
نویسندگان
چکیده
A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli.
منابع مشابه
Neomycin biosynthesis: the incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis.
D-[6-3H3]6-Deoxy-5-ketoglucose (10) and D-[5,6-3H2]6-deoxyglucose (11) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. D-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor D-glucose, and was found to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the pre...
متن کاملA short and scalable route to orthogonally O-protected 2-deoxystreptamine.
A seven-step synthesis of orthogonally O-protected 2-deoxy-streptamine has been developed from readily available neomycin, with an overall yield of 28%. Key chemical transformations include a chemoselective glycosidic bond hydrolysis and two regioselective protective group manipulations involving acetylation and deacetylation. The synthetic route is amenable to scale-up for the production of mu...
متن کاملProbing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.
Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin...
متن کاملMolecular cloning of the gene for the key carbocycle-forming enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics and its comparison with dehydroquinate synthase.
The 2-deoxystreptamine aglycon is a common structural feature found in aminocyclitol antibiotics including neomycin, kanamycin, tobramycin, gentamicin, sisomicin, butirosin and ribostamycin. A key enzyme involved in the biosynthesis of the 2-deoxystreptamine moiety is 2-deoxy-scyllo-inosose (DOI) synthase which catalyses the carbocycle formation from D-glucose-6-phosphate to 2-deoxy-scyllo-inos...
متن کاملNovel acyclic deoxystreptamine mimetics targeting the ribosomal decoding site.
KEYWORDS: aminoglycosides ¥ antibiotics ¥ drug design ¥ medicinal chemistry ¥ RNA recognition Natural aminoglycoside antibiotics such as paromomycin and neomycin B [1] disrupt functional protein synthesis in bacteria by specifically binding to the decoding-site RNA in the 30S ribosomal subunit (Figure 1), [2] thereby interfering with mRNA decoding fidelity and ultimately leading to bacterial ce...
متن کامل