LEAPS-MPS: Synthesis, Structural Analysis, and Characterization of Opioid Cyclic Tetrapeptides

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。在这个由数学和物理科学理事会资助并设在化学部门的项目中，雷德兰兹大学的Michael Ferracane教授和他的学生将研究一系列相关环肽的结构、性质和阿片活性。这项研究将提高环肽结构的基础知识，同时评估支架的治疗潜力。值得注意的是，该项目将把新的软件/设备集成到雷德兰兹大学的研究和课程中，并将为来自代表性不足群体的六名本科生提供机会：(1)参与校园内外的研究项目，(2)参加一系列的专业发展练习，以及(3)通过校园项目指导类似的学生。Ferracane教授和他的学生将评估环四肽的构效关系，以更好地了解它们的化学结构、性质和作为阿片类药物的潜力。他们将进行化学合成、核磁共振分析、分子建模以及一系列测量溶解度、膜通透性和阿片受体结合的分析。人们认为，不同的构象赋予肽可溶于水、被动渗透膜和结合阿片受体的能力。联合工作将阐明环四肽的独特序列和环境如何影响其整体构象景观，然后将这些发现与测量的性质和阿片活性联系起来。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Michael Ferracane and his students at University of Redlands will study the structure, properties, and opioid activities of a series of related cyclic peptides. This research will improve fundamental knowledge of cyclic peptide structure while assessing the scaffold’s therapeutic potential. Notably, the project will integrate new software/equipment into research and coursework at Redlands, and it will provide six undergraduate students from underrepresented groups with the opportunity to (1) engage in research projects on and off campus, (2) participate in a series of scaffolded professional development exercises, and (3) mentor similar students through on-campus programs.Professor Ferracane and his students will assess the structure-activity relationship of cyclic tetrapeptides to better understand their chemical structure, properties, and potential as opioid therapeutics. They will perform chemical synthesis, NMR analysis, and molecular modeling as well as a series of assays that measure solubility, membrane permeability, and opioid receptor binding. It is believed that distinct conformations impart a peptide with the ability to be soluble in water, passively permeate membranes, and bind the opioid receptors. The combined work will illuminate how a cyclic tetrapeptide’s unique sequence and environment affect its overall conformational landscape and then relate these findings to measured properties and opioid activities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.