A Novel Magnetic Separation Method to Isolate Active Compounds from Complex Matrices

一种从复杂基质中分离活性化合物的新型磁分离方法

• 批准号: 1915873
• 负责人: Yuping Bao
• 金额: $ 44.23万
• 依托单位: University of Alabama Tuscaloosa
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1915873&HistoricalAwards=false
• 关键词: Novel; Magnetic; Separation; Method; Isolate

Natural products are rich in biologically active (bioactive) compounds and serve as great sources for drug discovery. One of the major challenges in screening drug leads from natural products is the lack of effective tools to identify and separate the bioactive compounds. This project will develop and characterize a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (a cluster of nanoparticles) for the separation and identification of bioactive compounds from natural products. This method overcomes limitations of costly and time-intensive conventional approaches and the nonspecific binding problems of magnetic bead separation techniques. The new approach is also broadly applicable to many different types of transmembrane drug targets. The success of this project will advance industrial processes for identification and extraction of new drug leads from complex samples. The impact of this project will be further enhanced through student-led educational and outreach activities, including: (a) establishing a goal-oriented training mechanism and relevant course work for undergraduate researchers and (b) developing a STEM lead the way program with an emphasis on math concept building. Specific science outreach projects to be developed are Science middle school-targeted Olympiad training modules and magnetic fishing experiments for elementary school students through the "Science Party for Kids" program. The objective of this project is to develop a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (CSMPs) for the identification and separation of bioactive compounds from natural products. CSMPs will feature immobilized cell membranes with fully functional receptors that allow for identification of compounds specifically binding to the transmembrane receptors. The full encapsulation of magnetic superparticles inside a cell membrane overcomes the non-specific binding problems associated with the current magnetic bead separation technology. The use of magnetic superparticles enables rapid identification and extraction of compounds targeting transmembrane proteins. The CSMP approach is also easily translated to different transmembrane protein targets, which significantly broadens the applicability of this separation technique. Toward the overall objective, the PIs will develop, characterize, and evaluate the CSMP approach using cell membranes with functional nicotinic receptors to effectively identify binding compounds both in an artificial mixture (known binders and non-binders) and cigarette smoke condensates. The technique will be further verified using cell membranes with functional transient receptor potential (TRP) channels (e.g., TRPV1) and voltage-gated sodium channels. Both types of receptors have been shown as valid targets for the development of novel analgesic drugs. The outcome of the project will be fundamental knowledge related to efficient separation of bioactive compounds from complex matrices.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.

天然产物含有丰富的生物活性(生物活性)化合物，是药物发现的重要来源。从天然产物中筛选药物先导化合物的主要挑战之一是缺乏有效的工具来识别和分离生物活性化合物。本项目将开发和表征一种基于细胞膜包裹的氧化铁超微粒(一组纳米颗粒)的新的磁分离方法，用于从天然产物中分离和鉴定生物活性物质。这种方法克服了昂贵且耗时的传统方法的局限性和磁珠分离技术的非特异性结合问题。新的方法也广泛适用于许多不同类型的跨膜药物靶点。该项目的成功将推动从复杂样品中识别和提取新药先导的工业化进程。该项目的影响将通过学生主导的教育和外展活动进一步加强，包括：(A)为本科生研究人员建立以目标为导向的培训机制和相关的课程工作，以及(B)开发STEM Lead Way计划，重点是数学概念的建立。将开发的具体科学推广项目包括以科学中学为目标的奥林匹克训练模块，以及通过“儿童科学派对”计划为小学生进行的磁力钓鱼实验。本项目的目标是开发一种基于细胞膜包裹的氧化铁超微粒(CSMPs)的新的磁分离方法，用于从天然产物中鉴定和分离生物活性物质。CSMPs将以具有全功能受体的固定化细胞膜为特色，从而能够识别与跨膜受体特异结合的化合物。磁性超微粒完全包裹在细胞膜内，克服了与当前磁珠分离技术相关的非特异性结合问题。磁性超微粒的使用使快速鉴定和提取以跨膜蛋白为靶标的化合物成为可能。CSMP方法还可以很容易地转换为不同的跨膜蛋白靶标，这大大拓宽了这种分离技术的适用性。为了实现总体目标，PIS将开发、表征和评估CSMP方法，该方法使用带有功能尼古丁受体的细胞膜，有效地识别人工混合物(已知粘合剂和非粘合剂)和香烟烟雾冷凝物中的结合化合物。这项技术将使用具有功能的瞬时受体电位(Trp)通道(例如，TRPV1)和电压门控钠通道的细胞膜进一步验证。这两种受体已被证明是开发新型止痛药的有效靶点。该项目的成果将是与有效分离复杂物质中的生物活性化合物相关的基础知识。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Identification of TrkB Binders from Complex Matrices Using a Magnetic Drug Screening Nanoplatform

• DOI: 10.1021/acsabm.1c00552
• 发表时间: 2021-07-26
• 期刊: ACS APPLIED BIO MATERIALS
• 影响因子: 4.7
• 作者: Arituluk，Zekiye Ceren;Horne，Jesse;Bao，Yuping
• 通讯作者: Bao，Yuping

How addition of a nickel cyclohexyl-salen complex impacts a one-pot synthesis of nickel/hierarchically porous carbon monolith catalyst

• DOI: 10.1007/s10971-020-05436-3
• 发表时间: 2020-11
• 期刊: Journal of Sol-Gel Science and Technology
• 影响因子: 2.5
• 作者: Rina Adhikari;Trupti V. Kotbagi;K. H. Shaughnessy;Ambar B. Shrestha;J. Sherwood;Y. Bao;M. Bakker

Cell-membrane coated iron oxide nanoparticles for isolation and specific identification of drug leads from complex matrices

• DOI: 10.1039/c9nr01292c
• 发表时间: 2019-04-07
• 期刊: NANOSCALE
• 影响因子: 6.7
• 作者: Sherwood, Jennifer;Sowell, Josiah;Ciesla, Lukasz M.
• 通讯作者: Ciesla, Lukasz M.