Hollfelder F, Kirby A J, Tawfik D S
University Chemical Laboratory, Cambridge, United Kingdom.
Nature. 1996 Sep 5;383(6595):60-2. doi: 10.1038/383060a0.
Mimicking the efficiency of enzyme catalysis is a daunting challenge. An enzyme selectively binds and stabilizes the transition state (s) for a particular reaction. Artificial host systems can bind ground states just as efficiently, and rate enhancements comparable to those in enzymatic reactions can be achieved by bringing catalytic and substrate groups together in intramolecular reactions. But the combination of selective binding and efficient catalysis remains elusive. The best enzyme mimics currently known are catalytic antibodies. They bind transition-state analogues with high affinity, but their catalytic efficiency generally falls far short of that of enzymes. Thorn et al. recently described an antibody that catalyses the eliminative ring-opening of a benziosoxazole "exceptionally efficiently" using carboxylate as the general base, raising the intriguing possibility that this high efficiency derives from precise positioning of catalytic and substrate groups. Here we show that familiar 'off-the-shelf' proteins--serum albumins--catalyse the same reaction at similar rates, using a lysine side-chain amino group as the catalytic general base. Comparisons suggest that formal general base catalysis is of only modest efficiency in both systems, and that the antibody catalysis is boosted by a non-specific medium effect.
模仿酶催化的效率是一项艰巨的挑战。酶会选择性地结合并稳定特定反应的过渡态。人工主体系统能够同样高效地结合基态，并且通过在分子内反应中将催化基团和底物基团聚集在一起，可以实现与酶促反应相当的速率增强。但是，选择性结合和高效催化的结合仍然难以实现。目前已知的最佳酶模拟物是催化抗体。它们以高亲和力结合过渡态类似物，但其催化效率通常远低于酶。索恩等人最近描述了一种抗体，该抗体使用羧酸盐作为通用碱，“极其高效地”催化苯并异恶唑的消除开环反应，这引发了一种有趣的可能性，即这种高效率源于催化基团和底物基团的精确定位。在这里，我们表明，常见的“现成”蛋白质——血清白蛋白——使用赖氨酸侧链氨基作为催化通用碱，以相似的速率催化相同的反应。比较表明，在这两个系统中，形式上的通用碱催化效率都只是中等，并且抗体催化受到非特异性介质效应的促进。
