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

美国-瑞士主客体化学分子识别合作研究：酶和激素模拟物的设计与合成

• 批准号: 8813857
• 负责人: Carol Venanzi
• 金额: $ 1.1万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-15 至 1992-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8813857&HistoricalAwards=false
• 关键词: U.S.; Switzerland; Cooperative; Research; Molecular

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.

该奖项支持新泽西理工学院化学系的 Carol A. Venanzi 与苏黎世瑞士联邦理工学院生物技术系的 Jean-Luc Fauchere 以及日内瓦大学医院内分泌科的 Michel Vallotton 的合作。 他们研究的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。 要研究的模型系统是促肾上腺皮质激素（ACTH）的循环类似物。 选择这种分子是因为它既可以充当宿主（酶模拟物）又可以充当客体（激素模拟物）。 美国研究人员将使用分子建模技术与分子动力学模拟相结合，提供有关所提出的模拟物的分子识别特征的信息，例如与胰凝乳蛋白酶相比的催化成分的方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。 合作的优势在于，研究人员为该项目带来了计算机建模和实验研究方面明显互补的技能，以及对彼此方法的理解和欣赏。 拟议的研究涉及分子化学物理的一个具有挑战性且重要的领域。 这些结果将通过提供有关酶活性位点底物识别机制的信息以及有关激素受体分子识别要求的信息，有助于更好地了解酶的结构和生物催化活性。 酶和激素模拟物的成功合成将极大地有助于创造更便宜、也许更好的这些生物材料的替代品。