Construction of molecular switching system based on dipeptide framework

二肽序列α-氨基异丁酰-L-脯氨酸（Aib-L-Pro）仅采用两种构象，即，一种折叠（β-转角）构象和一种未折叠而延伸的构象。基于这种独特的性质，尝试利用基于Aib-L-Pro的二肽构建分子开关系统。设计了侧链氨基被保护的二肽，在其上引入功能基团以使它们能够协同工作。通过保护的L/D-α，γ-二氨基-α-甲基丁酸（L/D-MeDab）衍生物与保护的L-4α/β-氨基脯氨酸[L-Pro（4β-NH_2）]衍生物的偶联，合成了Boc-DL-DabMe（4-Cbz-NH）-L-Pro（4β-CbzNH）-OEt。至于可以表现和控制的功能，我们选择了两个Zn（II）-络合的bispicolylamino基团的合作功能，以切割磷酸二酯键的核糖核苷酸模型底物。活性可以通过使用末端间主客体包含的二肽的构象控制来控制。

The dipeptide sequence α-aminoisobutyryl-L-proline (Aib-L-Pro) adopts only two conformations, i.e., a folded (β-turn) conformation and an unfolded rather extended conformation. Based on this unique nature, it was attempted to utilize the Aib-L-Pro-based dipeptide for the construction of molecular switching system. The protected dipeptides possessing protected amino group in each side chain was designed, to which functional groups could be introduced for enabling their cooperative functioning. By the coupling of protected L/D-α,γ-diamino-α-methylbutyric acid (L/D-MeDab) derivative and protected L-4α/β-aminoproline [L-Pro(4β-NH_2] derivative, Boc-DL-DabMe(4-Cbz-NH)-L-Pro(4β-CbzNH)-OEt was synthesized. As for the function which could be manifested and controlled, we have chosen cooperative functioning of two Zn(II)-complexed bispicolylamino groups to cleave phosphodiester linkage of ribonucleotide model substrate. The activity could be controlled by conformational control of the dipeptide using interterminal host-guest inclusion.