Zhu Junfei, Li Zhiwen, Wang Qi, Liu Yang, He Junlin
College of Life Science, Guizhou University, Guiyang 550025, China.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; Hununbeier People's Hospital, Hununbeier 021008, China.
Bioorg Med Chem Lett. 2016 Sep 15;26(18):4462-4465. doi: 10.1016/j.bmcl.2016.07.076. Epub 2016 Jul 30.
In the catalytic core of 10-23 DNAzyme, its five adenine residues are moderate conservative, but with highly conserved functional groups like 6-amino group and 7-nitrogen atom. It is this critical conservation that these two groups could be modified for better contribution. With 2'-deoxyadenosine analogues, several functional groups were introduced at the 6-amino group of the five adenine residues. 3-Aminopropyl substituent at 6-amino group of A15 resulted in a five-fold increase of kobs. More efficient DNAzymes are expected by delicate design of the linkage and the external functional groups for this 6-amino group of A15. With this modification approach, other functional groups or residues could be optimized for 10-23 DNAzyme.
在10-23脱氧核酶的催化核心中,其五个腺嘌呤残基具有一定程度的保守性,但带有如6-氨基和7-氮原子等高度保守的官能团。正是这种关键的保守性使得这两个基团能够被修饰以发挥更好的作用。利用2'-脱氧腺苷类似物,在五个腺嘌呤残基的6-氨基上引入了几个官能团。A15的6-氨基上的3-氨丙基取代导致表观一级反应速率常数(kobs)增加了五倍。通过对A15的这个6-氨基的连接和外部官能团进行精细设计,有望得到更高效的脱氧核酶。采用这种修饰方法,10-23脱氧核酶的其他官能团或残基也可以得到优化。