CATALYSIS AND MECHANISM

前提是生物有机化学中激进的新方向 不太可能由大环模型系统的进一步阐述产生， 我们已经开始了一项计划，从新的分子设计催化剂， 形状. 因此，我们已经开发出结构基序， 可以以模块化方式制备各种裂缝状分子。 这些化合物的特征在于催化有用的官能团， 为高能中间体的过渡态提供补充。 它们的酸碱性类似于许多酶的活性位点 功能组的特征和呈现。 这些都准备好了 协同催化，但通过使用 刚性间隔元件。 现实的阵列开发用于合成 核酸酶、蛋白酶、歧化酶和氧桥二铁中心。 预计这些研究将继续有助于 合理药物设计的机制和结构基础。

With the premise that radical new departures in bioorganic chemistry are unlikely to result from further elaboration of macrocyclic model systems, we have embarked on a program to devise catalysts from new molecular shapes. Accordingly, we have developed structural motifs from which a variety of cleft-like molecules can be prepared in modular fashion. These feature catalytically useful functional groups which converge to provide complements to transition states of high-energy intermediates. They resemble a number of enzyme active sites in their acid-base character and presentation of functional groups. These are poised for concerted catalysis, but kept from direct interaction through the use of rigid spacer elements. Realistic arrays are developed for synthetic nucleases, proteases, dismutases and oxobridged diiron centers. It is expected that these studies will continue to contribute to the mechanistic and structural foundations of rational drug design.