To design and synthesize neamine analogues modified at 5 position offing Ⅱ, which could improve the binding affinity of aminoglycosides to 16S RNA. Started from neomycin B, modified neamine analogues were synthesized...To design and synthesize neamine analogues modified at 5 position offing Ⅱ, which could improve the binding affinity of aminoglycosides to 16S RNA. Started from neomycin B, modified neamine analogues were synthesized through organic reactions such as hydrolysis, protection, nucleophilic substitution, deprotection and reduction. The interaction of the target compounds with A-site RNA in E. coli. ribosome （16S RNA） was determined by surface plasmon resonance （SPR）, respectively. Six target compounds were synthesized. Some of them showed antibacterial activities and enhanced affinity to 16S RNA at 10^-3M in vitro. Introduction amino or aliphatic amino group at 5 position offing Ⅱ in neamine would maintained antibacterial activities as well as increase binding affinity to 16S RNA. Furthermore, there is almost no influence on the stability of drug/16S RNA complex by inverting the configuration of 5-hydroxyl group at ring Ⅱ.展开更多
基金National Natural Science Foundation of China(Grant No.20332010)the Ministry of Science and Technology of China(Grant No.2005BA711A04).
文摘To design and synthesize neamine analogues modified at 5 position offing Ⅱ, which could improve the binding affinity of aminoglycosides to 16S RNA. Started from neomycin B, modified neamine analogues were synthesized through organic reactions such as hydrolysis, protection, nucleophilic substitution, deprotection and reduction. The interaction of the target compounds with A-site RNA in E. coli. ribosome （16S RNA） was determined by surface plasmon resonance （SPR）, respectively. Six target compounds were synthesized. Some of them showed antibacterial activities and enhanced affinity to 16S RNA at 10^-3M in vitro. Introduction amino or aliphatic amino group at 5 position offing Ⅱ in neamine would maintained antibacterial activities as well as increase binding affinity to 16S RNA. Furthermore, there is almost no influence on the stability of drug/16S RNA complex by inverting the configuration of 5-hydroxyl group at ring Ⅱ.
