U.S.-Switzerland Cooperative Research on Molecular Recognition in Host-Guest Chemistry: The Design and Synthesis of Enzyme and Hormone Mimics

该奖项支持卡罗尔A。化学系的Venanzi， 新泽西理工学院，与让-吕克合作 瑞士联邦研究所生物技术系的福谢尔 苏黎世技术司和Michel Vallotton 日内瓦大学医院内分泌科。 目标的事业中 研究是为了了解相对贡献 分子的结构和静电成分 识别到主体-客体络合过程。 模型系统 是一种促肾上腺皮质激素的环状类似物 （ACTH）。 选择这个分子是因为它既可以作为宿主 （酶模拟物）和客体（激素模拟物）。 美国调查员 将使用分子建模技术， 动力学模拟提供分子信息 建议模仿的识别特征，如方向 与胰凝乳蛋白酶相比， 溶剂对构象的影响。 瑞士调查人员将 合成并测试目标分子的生物活性。 合作的好处是，调查人员带来了 该项目在计算机建模方面具有明显的互补性， 实验研究沿着理解和欣赏 彼此的方法。 拟议的研究解决了一个具有挑战性和重要的领域， 分子化学物理 结果将有助于更好地 了解酶的结构和生物催化活性 通过提供关于底物识别机制的信息， 酶的活性位点，以及有关要求的信息 用于激素受体的分子识别。 成功 酶和激素模拟物的合成将大大有助于 创造更便宜，也许更好的替代品， 生物材料

This award supports Carol A. Venanzi of the Department of Chemistry, New Jersey Institute of Technology, for collaboration with Jean-Luc Fauchere of the Department of Biotechnology, Swiss Federal Institute of Technology, Zurich and Michel Vallotton, Division of Endocrinology, University Hospital, Geneva. The objective of their research is to obtain an understanding of the relative contributions of the structural and electrostatic components of molecular recognition to the host-guest complexation process. The model system to be studied is a cyclic analog of adrenocorticotropic hormone (ACTH). This molecule was chosen because it can act as both a host (enzyme mimic) and a guest (hormone mimic). The U.S. investigator will use molecular modeling techniques combined with molecular dynamics simulations to provide information on the molecular recognition features of the proposed mimic, such as the orientation of the catalytic components as compared to chymotrypsin and the effect of solvent on conformation. The Swiss investigators will synthesize and test the biological activity of the target molecule. The advantage of the collaboration is that the investigators bring to the project distinctly complementary skills in computer modelling and experimental research along with an understanding and an appreciation of each other's methods. The proposed research addresses a challenging and important area of molecular chemical physics. The results will contribute to a better understanding of the structure and biocatalytic activity of enzymes by providing information on the mechanism of substrate recognition at the enzyme active site, as well as information on the requirements for molecular recognition at the hormone receptor. The successful synthesis of enzyme and hormone mimics will contribute greatly to the creation of cheaper and perhaps better substitutes for these biomaterials.