Poulin-Kerstien Adam T, Dervan Peter B
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
J Am Chem Soc. 2003 Dec 24;125(51):15811-21. doi: 10.1021/ja030494a.
Double-helical DNA accelerates the rate of ligation of two six-ring hairpin polyamides which bind adjacent sites in the minor groove via a 1,3-dipolar cycloaddition to form a tandem dimer. The rate of the templated reaction is dependent on DNA sequence as well as on the distance between the hairpin-binding sites. The tandem dimer product of the DNA-templated reaction has improved binding properties with respect to the smaller hairpin fragments. Since cell and nuclear uptake of DNA-binding polyamides will likely be dependent on size, this is a minimum first step toward the design of self-assembling small gene-regulating fragments to produce molecules of increasing complexity with more specific genomic targeting capabilities.
双螺旋DNA加速了两个六环发夹型聚酰胺的连接速率，这两个聚酰胺通过1,3-偶极环加成反应结合在小沟中的相邻位点，形成串联二聚体。模板反应的速率取决于DNA序列以及发夹结合位点之间的距离。与较小的发夹片段相比，DNA模板反应的串联二聚体产物具有更好的结合特性。由于与DNA结合的聚酰胺的细胞和细胞核摄取可能取决于大小，这是朝着设计自组装小基因调控片段迈出的最小的第一步，以产生具有更特异基因组靶向能力的、复杂性不断增加的分子。
