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

LEAPS-MPS：阿片类环状四肽的合成、结构分析和表征

• 批准号: 2213528
• 负责人: Michael Ferracane
• 金额: $ 24.93万
• 依托单位: University of Redlands
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2213528&HistoricalAwards=false
• 关键词: LEAPS; MPS; Synthesis; Structural; Analysis

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.

该奖项全部或部分根据2021年美国救援计划法案（公法117-2）资助。 在这个项目中，由数学和物理科学理事会资助，并设在化学部，教授迈克尔Ferracane和他的学生在雷德兰兹大学将研究的结构，性质和阿片类药物活性的一系列相关的环肽。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/设备整合到雷德兰兹的研究和课程中，它将为来自代表性不足群体的六名本科生提供机会，（1）从事校内和校外的研究项目，（2）参加一系列脚手架专业发展练习，及（3）透过校内课程，指导同类学生。Ferracane教授及其学生将评估环四肽的构效关系，以更深入了解其化学结构、性质，和作为阿片类药物治疗剂的潜力。他们将进行化学合成，NMR分析和分子建模，以及一系列测量溶解度，膜渗透性和阿片受体结合的测定。据信，不同的构象赋予肽可溶于水、被动渗透膜并结合阿片受体的能力。结合工作将阐明如何环四肽的独特序列和环境影响其整体构象景观，然后将这些发现与测量的属性和阿片类药物activity.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。