Chiral introduction of positive charges to PNA for double-duplex invasion to versatile sequences
Chiral introduction of positive charges to PNA for double-duplex invasion to versatile sequences
复制标题
DOI：
10.1093/nar/gkm1154
复制
发表时间：
2008-03-01
影响因子：
14.9
通讯作者：
Komiyama, Makoto
中科院分区：
文献类型：
--
作者：
Ishizuka, Takumi;Yoshida, Junya;Komiyama, Makoto
双肽核酸（PNA）侵入双链DNA是识别双链DNA中预定位点（PNA肽核酸）的最有前途的方法之一。为了促进这种双链体侵入，通过使用手性PNA单体制备新型PNA，其中核碱基与N-（2-氨乙基）-D-赖氨酸的-氮结合。这些带正电荷的单体单元，引入到Nielsens PNA（聚[N-（2-氨基乙基）甘氨酸]衍生物）中的定义位置，促进了入侵而不损害错配识别活性。当假互补核碱基2，6-二氨基嘌呤和2-硫尿嘧啶与N-（2-氨乙基）-D-赖氨酸结合时，即使在GC高度富集的区域[例如（G/C）7（A/T）3和（G/C）7（A/T）3和（G/C）8（A/T）2]也成功发生入侵，否则这些区域很难被靶向。因此，可用作靶位点的序列的范围已经大大扩展。与来自N-（2-氨乙基）-D-赖氨酸的手性PNA单体的促进作用相反，它们的L-异构体几乎不侵入，显示出D-手性的至关重要性。手性（D）PNA单体单元促进双链体侵入归因于PNA/PNA双链体的不稳定和PNA/DNA双链体的稳定。
Invasion of two PNA strands to double-stranded DNA is one of the most promising methods to recognize a predetermined site in double-stranded DNA (PNA peptide nucleic acid). In order to facilitate this double-duplex invasion, a new type of PNA was prepared by using chiral PNA monomers in which a nucleobase was bound to the -nitrogen of N-(2-aminoethyl)-D-lysine. These positively charged monomer units, introduced to defined positions in Nielsens PNAs (poly[N-(2-aminoethyl)glycine] derivatives), promoted the invasion without impairing mismatch-recognizing activity. When pseudo-complementary nucleobases 2,6-diaminopurine and 2-thiouracil were bound to N-(2-aminoethyl)-D-lysine, the invasion successfully occurred even at highly GC-rich regions [e.g. (G/C)7(A/T)3 and (G/C)8(A/T)2] which were otherwise hardly targeted. Thus, the scope of sequences available as the target site has been greatly expanded. In contrast with the promotion by the chiral PNA monomers derived from N-(2-aminoethyl)-D-lysine, their L-isomers hardly invaded, showing crucial importance of the D-chirality. The promotion of double-duplex invasion by the chiral (D) PNA monomer units was ascribed to both destabilization of PNA/PNA duplex and stabilization of PNA/DNA duplexes.