Multivalent macrocyclic hosts: Histone surface recognition, guest binding, and delivery by cyclophane-based resorcinarene oligomers
Multivalent macrocyclic hosts: Histone surface recognition, guest binding, and delivery by cyclophane-based resorcinarene oligomers
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DOI：
10.1021/jo062229o
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发表时间：
2007-01-19
影响因子：
3.6
通讯作者：
Uchiyama, Masaki
中科院分区：
文献类型：
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作者：
Hayashida, Osamu;Uchiyama, Masaki
[图]作为特定蛋白质和疏水分子客体的新型宿主，基于环芳烷的间苯二芳烃低聚物的设计基于允许在环芳骨架上组装 4 个或 12 个阴离子间苯二芳烃的分子设计。我们制备了一种基于环芳烷的间苯二芳烃四聚体 (4)，由四氮杂[6.1.6.1]-对环芳烷骨架和四个带有通过酰胺键连接到大环的七羧酸残基的间苯二芳烃构成。此外，我们还制备了一个扩展的类似十二聚体（12），它由五环芳烷骨架和12个间苯二芳烃构成。基于环芳烷的间苯二酚低聚物对组蛋白（真核染色质的一种小型碱性蛋白）表现出有效的识别能力。通过表面等离子体共振测量，基于环芳烷的间苯二酚四聚体4和十二聚体12与组蛋白的结合常数(K)分别确定为1.3 x 10(7)和8.4 x 10(7) M-1。含有组蛋白的 4 和 12 的 K 值比未束缚的参考间苯二酚大 31 倍和 200 倍，反映了间苯二酚的多价效应。除此之外，基于环芳烷的间苯二酚四聚体 4 和十二聚体 12 捕获了疏水性客体，例如 6-对甲苯胺萘-2-磺酸盐，通过荧光光谱法评估，在水性 HEPES 缓冲液中的结合常数分别为 2.4 x 10(3) 和 2.5 x 10(4) M-1。此外，正如荧光光谱所证实的那样，间苯二酚低聚物也被发现充当从本体水相到组蛋白表面的客体载体。
[GRAPHIC]As a new class of host for both specific proteins and hydrophobic molecular guests, cyclophane-based resorcinarene oligomers were designed on the basis of a molecular design that allows the assembly of four or 12 anionic resorcinarenes on a cyclophane skeleton. We prepared a cyclophane-based resorcinarene tetramer (4), constructed with a tetraaza[6.1.6.1]-paracyclophane skeleton and four resorcinarenes bearing heptacarboxylic acid residues that connect to the macrocycle through amide linkages. In addition, we prepared an extended analogical dodecamer (12), which was constructed with a pentakis(cyclophane) skeleton and 12 resorcinarenes. The cyclophane-based resorcinarene oligomers exhibited potent recognition capabilities toward histone, a small basic protein of eukaryotic chromatins. The binding constants (K) of cyclophane-based resorcinarene tetramer 4 and dodecamer 12 with histone were determined to be 1.3 x 10(7) and 8.4 x 10(7) M-1, respectively, by means of surface plasmon resonance measurements. The K values of 4 and 12 with histone were 31- and 200-fold larger than that of an untethered reference resorcinarene, reflecting the multivalency effects in resorcinarenes. In addition to that, cyclophane-based resorcinarene tetramer 4 and dodecamer 12 captured hydrophobic guests such as 6-p-toluidinonaphthalene-2-sulfonate, with respective binding constants of 2.4 x 10(3) and 2.5 x 10(4) M-1 in an aqueous HEPES buffer as evaluated by fluorescence spectroscopy. Furthermore, the resorcinarene oligomers were also found to act as guest carriers from the bulk aqueous phase to histone surfaces, as confirmed by fluorescence spectroscopy.