Multivalency in the recognition and antagonism of a HIV TAR RNA-TAT assembly using an aminoglycoside benzimidazole scaffold.
Multivalency in the recognition and antagonism of a HIV TAR RNA-TAT assembly using an aminoglycoside benzimidazole scaffold.
复制标题
DOI：
10.1039/c5ob02016f
复制
发表时间：
2016-02-14
影响因子：
3.2
通讯作者：
Arya DP
中科院分区：
文献类型：
--
作者：
Kumar S;Ranjan N;Kellish P;Gong C;Watkins D;Arya DP
通过高亲和力结合小分子识别RNA对于扩展RNA识别中的现有方法和开发新型RNA结合药物至关重要。通过点击化学将新霉素二聚体与苯并咪唑炔缀合以靶向HIV TAR RNA上的多个结合位点，合成了新型新霉素二聚体苯并咪唑缀合物5（DPA 83）。配体5显著增强了HIV TAR RNA的热稳定性，并以低纳摩尔亲和力与HIV TAR RNA化学计量地相互作用。5显示出比其单独的结构单元（包括新霉素二聚体叠氮化物和苯并咪唑炔）增强的结合。本质上，设计并合成了高亲和力多价配体以靶向HIV TAR RNA。
Recognition of RNA by high-affinity binding small molecules is crucial for expanding existing approaches in RNA recognition, and for the development of novel RNA binding drugs. A novel neomycin dimer benzimidazole conjugate 5 (DPA 83) was synthesized by conjugating a neomycin-dimer with benzimidazole alkyne using click chemistry to target multiple binding sites on HIV TAR RNA. Ligand 5 significantly enhances the thermal stability of HIV TAR RNA and interacts stoichiometrically with HIV TAR RNA with a low nanomolar affinity. 5 displayed enhanced binding than its individual building blocks including neomycin dimer azide and benzimidazole alkyne. In essence, a high affinity multivalent ligand was designed and synthesized to target HIV TAR RNA.