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

该奖项支持新泽西理工学院化学系的Carol A.Venanzi与瑞士联邦理工学院苏黎世生物技术系的Jean-Luc Fuchhere和日内瓦大学医院内分泌科的Michel Vallotton合作。他们的研究目的是了解分子识别的结构和静电成分对主客体络合过程的相对贡献。被研究的模型体系是促肾上腺皮质激素(ACTH)的环状类似物。之所以选择这种分子，是因为它既可以作为宿主(模拟酶)，也可以作为客体(模拟激素)。这位美国研究人员将使用分子建模技术结合分子动力学模拟来提供有关拟议模拟物的分子识别特征的信息，例如与糜蛋白酶相比催化组分的取向以及溶剂对构象的影响。瑞士研究人员将合成并测试目标分子的生物活性。这种合作的好处是，研究人员为该项目带来了计算机建模和实验研究方面的明显互补技能，以及对彼此方法的理解和欣赏。这项拟议的研究涉及分子化学物理中一个具有挑战性和重要的领域。这些结果将有助于更好地了解酶的结构和生物催化活性，提供关于酶活性部位底物识别机制的信息，以及关于激素受体分子识别要求的信息。酶和激素模拟物的成功合成将大大有助于创造出更便宜、甚至更好的这些生物材料的替代品。

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.