CONTROL OF FOLDING AND BINDING OF OLIGONUCLEOTIDES BY USE OF A NONNUCLEOTIDE LINKER

CONTROL OF FOLDING AND BINDING OF OLIGONUCLEOTIDES BY USE OF A NONNUCLEOTIDE LINKER
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DOI:
10.1021/ja00049a003
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发表时间:
1992-11-04
影响因子:
15
通讯作者:
LETSINGER, RL
LETSINGER, RL
中科院分区:
化学1区
文献类型:
--
作者:
SALUNKHE, M;WU, TF;LETSINGER, RL

文献摘要

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含有N-乙酰氨基-P(O)(O-)O(CH 2)6 NHC(O)C6 H4 C(O)NH(CH 2)6 OP(O)(O-)-的接头被证明是在溶液中组织寡核苷酸链的有效结构元件。用该接头加帽一对互补寡核苷酸导致沃森-克里克双链体结构的稳定性显著增强。将一对胸苷酸寡聚体与该连接体连接得到对寡聚体(dA)链表现出异常高的亲和力的化合物;甚至可以在稀溶液中识别四聚体单元。据推测,Hoogsteen以及沃森-克里克氢键稳定了双分子的“三链体”。两种类型的链接(即,连接两条互补链和连接两条嘧啶链)体现在新化合物d(TTTTTT-X-TTTTTT-X-AAAAAA)中,并共同起稳定双重折叠的单分子三链结构的作用(T(m)58 ℃,1 M NaCl; -X-代表N-异烟酰胺连接基团)。
A linker containing a terephthalamide group, -P(O)(O-)O(CH2)6NHC(O)C6H4C(O)NH(CH2)6OP(O)(O-)-, is shown to be an effective structural element for organizing oligonucleotide chains in solution. Capping a pair of complementary oligonucleotides with this linker leads to marked enhancement in stability of the Watson-Crick duplex structure. Joining a pair of thymidylate oligomers with this linker gives a compound exhibiting unusually high affinity for oligo(dA) strands; even a tetramer unit can be recognized in dilute solution. Presumably Hoogsteen as well as Watson-Crick hydrogen bonding stabilizes a bimolecular 'triplex". Both types of linkage (i.e., joining two complementary strands and joining two pyrimidine strands) are embodied in the novel compound, d(TTTTTT-X-TTTTTT-X-AAAAAA), and function jointly in stabilizing a doubly folded monomolecular triple stranded structure (T(m) 58-degrees-C, 1 M NaCl; -X- represents the terephthalamide linker group).