Controlling the biological effects of spermine using a synthetic receptor

被引:101
作者
Vial, Laurent [1 ]
Ludlow, R. Frederick [1 ]
Leclaire, Julien [1 ]
Perez-Fernandez, Ruth [1 ]
Otto, Sijbren [1 ]
机构
[1] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England
基金
英国工程与自然科学研究理事会;
关键词
D O I
10.1021/ja062536b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to compete with biological polyamine receptors remains a huge challenge. Binding affinities of synthetic hosts are typically separated by a gap of several orders of magnitude from those of biomolecules. We now report that a dynamic combinatorial selection approach can deliver a synthetic receptor that bridges this gap. The selected receptor binds spermine with a dissociation constant of 22 nM, sufficient to remove it from its natural host DNA and reverse some of the biological effects of spermine on the nucleic acid. In low concentrations, spermine induces the formation of left-handed DNA, but upon addition of our receptor, the DNA reverts back to its right-handed form. NMR studies and computer simulations suggest that the spermine complex has the form of a pseudo-rotaxane. The spermine receptor is a promising lead for the development of therapeutics or molecular probes for elucidating spermine's role in cell biology.
引用
收藏
页码:10253 / 10257
页数:5
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