OLIGONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATES
OLIGONUCLEOTIDE N3'-]P5' PHOSPHORAMIDATES
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DOI：
10.1073/pnas.92.13.5798
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发表时间：
1995-06-20
影响因子：
11.1
通讯作者：
WILSON, WD
中科院分区：
文献类型：
--
作者：
GRYAZNOV, SM;LLOYD, DH;WILSON, WD
人工合成的寡核苷酸及其类似物最近引起了人们的极大兴趣，这些化合物可能导致高度特异的治疗药物以及强大的诊断工具。在这里，我们合成了含有3‘-NHP(O)(O-)O-5’核苷键的均匀修饰的寡核苷酸N3‘->；P5’磷酰亚胺，并研究了它们的杂交性质。热分解实验表明，这些化合物与单链DNA、RNA形成了非常稳定的双链，并且经过Watson-Crick碱基配对后，双链热稳定性比磷酸二酯提高了2.2-2.6℃。由磷酰亚胺形成的络合物的结构与RNA低聚体的结构非常相似，对应于A型，CD光谱判断，N3‘->；P5’在近生理条件下也与双链DNA形成稳定的三链体，当天然磷二酸酯不能形成时，其物理化学特征与RNA低聚体相似，尽管它们是由2‘-脱氧呋喃糖基核苷组成的。
Synthetic oligonucleotides and their analogs have attracted considerable interest recently, These compounds may lead to highly specific therapeutic agents, as well as to powerful diagnostic tools, Here, we present the synthesis of uniformly modified oligodeoxyribonucleotide N3' --> P5' phosphoramidates containing 3'-NHP(O)(O-)O-5' internucleoside linkages and the study of their hybridization properties, Thermal dissociation experiments show that these compounds form very stable duplexes with single-stranded DNA, RNA, and with themselves following Watson-Crick base pairing, The duplex thermal, stability was enhanced by 2.2-2.6 degrees C per modified linkage compared with phosphodiesters. The structure of complexes formed by phosphoramidates closely resembles that of RNA oligomers and corresponds to an A form, as judged by CD spectroscopy, N3' --> P5' phosphoramidates also form stable triplexes with double-stranded DNA under near-physiological conditions when natural phosphodiesters fail to do so, Physicochemical characteristics of the amidates are similar to those of RNA oligomers, even though they are composed of 2'-deoxyfuranose-based nucleosides.