Peck Evan M, Liu Wenqi, Spence Graeme T, Shaw Scott K, Davis Anthony P, Destecroix Harry, Smith Bradley D
†Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
‡School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, U.K.
J Am Chem Soc. 2015 Jul 15;137(27):8668-71. doi: 10.1021/jacs.5b03573. Epub 2015 Jun 29.
A macrocyclic tetralactam host is threaded by a highly fluorescent squaraine dye that is flanked by two polyethylene glycol (PEG) chains with nanomolar dissociation constants in water. Furthermore, the rates of bimolecular association are very fast with k(on) ≈ 10(6)-10(7) M(-1) s(-1). The association is effective under cell culture conditions and produces large changes in dye optical properties including turn-on near-infrared fluorescence that can be imaged using cell microscopy. Association constants in water are ∼1000 times higher than those in organic solvents and strongly enthalpically favored at 27 °C. The threading rate is hardly affected by the length of the PEG chains that flank the squaraine dye. For example, macrocycle threading by a dye conjugate with two appended PEG2000 chains is only three times slower than threading by a conjugate with triethylene glycol chains that are 20 times shorter. The results are a promising advance toward synthetic mimics of streptavidin/biotin.
一种大环四内酰胺主体分子被一种高荧光方酸染料贯穿，该染料两侧带有两条聚乙二醇（PEG）链，在水中具有纳摩尔级的解离常数。此外，双分子缔合速率非常快，k(on)≈10(6)-10(7) M(-1) s(-1)。这种缔合在细胞培养条件下是有效的，并会使染料的光学性质发生很大变化，包括开启近红外荧光，可通过细胞显微镜成像。在水中的缔合常数比在有机溶剂中高约1000倍，在27°C时强烈受焓的影响。贯穿速率几乎不受方酸染料两侧PEG链长度的影响。例如，由带有两条附加PEG2000链的染料共轭物进行的大环贯穿，仅比由链长短20倍的三甘醇链共轭物进行的贯穿慢三倍。这些结果是朝着链霉亲和素/生物素的合成模拟物迈出的有希望的一步。
