CAJ | 학술논문

为了提高新霉胺对16S rRNA的亲和力,合成了Ⅱ环5位修饰的新霉胺类似物.以新霉素B为原料,经水解,保护,亲核取代,脱保护,叠氮还原多步反应得到氨基或氨基链修饰的新霉胺类似物.用表面等离子共振法测定了所合成的化合物与大肠杆菌(E. coil)核糖体A位点rRNA(16S RNA)的相互作用.合成了6个Ⅱ环5-位修饰的新霉胺类似物,发现Ⅱ环5位氨基链修饰可以增强化合物对16S RNA的亲和力,其中一些化合物在10-3M有体外细菌抑制活性.在新霉胺的Ⅱ环5位引入氨基或脂肪胺可以增加与16S RNA的亲和力.Ⅱ环5位上羟基的构型改变对于药物/16S RNA复合物稳定性的影响较低.
위료제고신매알대16S rRNA적친화력,합성료Ⅱ배5위수식적신매알유사물.이신매소B위원료,경수해,보호,친핵취대,탈보호,첩담환원다보반응득도안기혹안기련수식적신매알유사물.용표면등리자공진법측정료소합성적화합물여대장간균(E. coil)핵당체A위점rRNA(16S RNA)적상호작용.합성료6개Ⅱ배5-위수식적신매알유사물,발현Ⅱ배5위안기련수식가이증강화합물대16S RNA적친화력,기중일사화합물재10-3M유체외세균억제활성.재신매알적Ⅱ배5위인입안기혹지방알가이증가여16S RNA적친화력.Ⅱ배5위상간기적구형개변대우약물/16S RNA복합물은정성적영향교저.
To design and synthesize neamine analogues modified at 5 position of ring Ⅱ, which could improve the binding affinity of aminoglycosides to 16S RNA. Started from neomycin B, modified neamine analogues were synthesized through organic reac- tions such as hydrolysis, protection, nucleophilic substitution, deprotection and reduction. The interaction of the target com- pounds 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 aliphatie amino group at 5 position of ring 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 com- plex by inverting the configuration of 5-hydroxyl group at ring Ⅱ.