Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Org Biomol Chem. 2011 Jan 7;9(1):243-52. doi: 10.1039/c0ob00532k. Epub 2010 Nov 3.
The synthesis of 2'-amino-LNA (the 2'-amino derivative of locked nucleic acid) has opened up a number of exciting possibilities with respect to modified nucleic acids. While maintaining the excellent duplex stability inferred by LNA-type oligonucleotides, the nitrogen in the 2'-position of 2'-amino-LNA monomers provides an excellent handle for functionalisation. Herein, the synthesis of amino acid functionalised 2'-amino-LNA derivatives is described. Following ON synthesis, a glycyl unit attached to the N2'-position of 2'-amino-LNA monomers was further acylated with a variety of amino acids. On binding to DNA/RNA complements, the modified ONs induce a marked increase in thermal stability, which is particularly apparent in a buffer system with a low salt concentration. The increase in thermal stability is thought to be caused, at least in part, by decreased electrostatic repulsion between the negatively charged phosphate backbones when positively charged amino acid residues are appended. Upon incorporation of more than one 2'-amino-LNA modification, the effects are found to be nearly additive. For comparison, 2'-amino-LNA derivatives modified with uncharged groups have been synthesised and their effect on duplex thermal stability likewise investigated.
2'-氨基-LNA（锁核酸的 2'-氨基衍生物）的合成在修饰核酸方面开辟了许多令人兴奋的可能性。2'-氨基-LNA 单体 2'-位的氮在保持 LNA 型寡核苷酸推断出的优异双链体稳定性的同时，为功能化提供了极好的处理手段。本文描述了氨基酸官能化 2'-氨基-LNA 衍生物的合成。在 ON 合成之后，连接到 2'-氨基-LNA 单体的 N2'-位的甘氨酰基单元进一步与各种氨基酸进行酰化。在与 DNA/RNA 互补物结合时，修饰的 ON 诱导热稳定性显著增加，在低盐浓度的缓冲系统中尤其明显。这种热稳定性的增加被认为至少部分是由于当附加正电荷的氨基酸残基时，带负电荷的磷酸骨架之间的静电排斥减少所致。当掺入一个以上的 2'-氨基-LNA 修饰时，发现这些效果几乎是可加的。相比之下，已经合成了用非电荷基团修饰的 2'-氨基-LNA 衍生物，并同样研究了它们对双链体热稳定性的影响。
