Grossmann Tom N, Sasaki Shunta, Ritzefeld Markus, Choi Sung Won, Maruyama Atsushi, Seitz Oliver
Institut für Chemie, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
Bioorg Med Chem. 2008 Jan 1;16(1):34-9. doi: 10.1016/j.bmc.2007.04.066. Epub 2007 May 6.
The uncharged DNA-analogue peptide nucleic acid (PNA) can invade into dsDNA by displacing the non-complementary DNA strand. The formed strand displacement complexes can create a sterical hindrance to block access of enzymes such as nucleases and polymerases. Due to the high stability of DNA.PNA duplexes it is usually not possible to displace the PNA strand by ssDNA or ssRNA. We herein report that the polycationic, comb-type copolymer alphaPLL-g-Dex can induce such a replacement of PNA in DNA.PNA duplexes by ssDNA. The influence of the copolymer on strand exchange highly depends on the nature of the oligonucleotides. Acceleration has only been observed when both the starting duplex and the single-stranded exchanger strand were negatively charged. The presented approach should allow the withdrawal of PNA induced sterical hindrance of DNA by rehybridisation with ssDNA.
不带电荷的DNA类似物肽核酸（PNA）可以通过取代非互补DNA链侵入双链DNA。形成的链置换复合物会产生空间位阻，以阻止核酸酶和聚合酶等酶的接近。由于DNA·PNA双链体的高稳定性，通常不可能通过单链DNA或单链RNA取代PNA链。我们在此报告，聚阳离子梳型共聚物αPLL-g-Dex可以诱导单链DNA取代DNA·PNA双链体中的PNA。共聚物对链交换的影响高度依赖于寡核苷酸的性质。只有当起始双链体和单链交换链都带负电荷时，才观察到加速现象。所提出的方法应该能够通过与单链DNA重新杂交来消除PNA对DNA的空间位阻。
