CAREER: Light- and temperature- controlled peptide ligands for purifying blood factors and orphan enzyme drugs

职业：用于纯化血液因子和孤儿酶药物的光控和温控肽配体

• 批准号: 1653590
• 负责人: Stefano Menegatti
• 金额: $ 50.99万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1653590&HistoricalAwards=false
• 关键词: CAREER; Light; temperature; controlled; peptide

Modern medicine has drastically increased the life span of our population, yet the cost of health care is very high, and has risen drastically over the past decade. Many Americans struggle with their monthly cost for prescription drugs. The production of pharmaceuticals is expensive, and a large portion of this production cost can be attributed to purification and isolation of a particular active component. The aim of this CAREER project is to develop a new method for purification of biologically-derived active components that increases selectivity while maintaining the activity of the drug, thereby decreasing the cost of drug purification. This project is aimed towards the development of a purification technology tailored for labile therapeutics, which are high-value drug biomolecules that rapidly and irreversibly lose their activity outside a narrow range of conditions in solution (such as pH or ionic strength). The project will develop a single aqueous solvent purification process that is controlled by external stimuli, e.g. light and temperature, relatively mild stimulations that will retain the activity of the biomolecules. New ligands will be developed that selectively captures two target biomolecules under visible light, or ambient temperature, and releases the drug in dark or cold. The newly developed ligands will be characterized in depth to allow for further product optimization and finally, validation of the technique by purifying target proteins from blood plasma and cell culture fluids. The use of such simple, external switches to trigger the capture and release of the product holds great promise to considerably reduce the process footprint as compared to current setups. The use of a single aqueous solvent not only ensures product bioactivity, but also enables significant process intensification. The research entails the development of tools that have the potential to stimulate other research areas, and lead to the discovery of novel ?smart? materials and diagnostics that will have a positive impact on the quality of life of future generations. One graduate student will be trained in this project, a high school teacher will be involved in the laboratory work, and the PI will leverage his appointment in a biomanufacturing education and training center to interact with local biotech industries and commercial the intellectual property from this work.

现代医学极大地延长了人们的寿命，但医疗保健的成本非常高，并且在过去十年中急剧上升。许多美国人为每月的处方药费用而苦苦挣扎。 药品的生产成本高昂，其中很大一部分生产成本可归因于特定活性成分的纯化和分离。 该CAREER项目的目的是开发一种纯化生物源活性成分的新方法，在保持药物活性的同时提高选择性，从而降低药物纯化成本。该项目旨在开发一种针对不稳定治疗药物的纯化技术，这些治疗药物是高价值的药物生物分子，在溶液中的狭窄条件范围（例如 pH 或离子强度）之外会迅速且不可逆地失去活性。 该项目将开发一种由外部刺激控制的单一水性溶剂纯化工艺，例如光和温度，相对温和的刺激将保留生物分子的活性。 将开发新的配体，在可见光或环境温度下选择性捕获两个目标生物分子，并在黑暗或寒冷下释放药物。新开发的配体将进行深入表征，以便进一步优化产品，最后通过从血浆和细胞培养液中纯化目标蛋白来验证技术。 与当前设置相比，使用这种简单的外部开关来触发产品的捕获和释放有望大大减少工艺足迹。使用单一水溶剂不仅可以确保产品的生物活性，而且可以显着强化工艺。该研究需要开发有潜力刺激其他研究领域的工具，并导致新的“智能”的发现。材料和诊断将对子孙后代的生活质量产生积极影响。该项目将培训一名研究生，一名高中教师将参与实验室工作，PI将利用他在生物制造教育和培训中心的任命与当地生物技术行业互动，并将这项工作的知识产权商业化。

项目成果

Photoinduced reconfiguration to control the protein-binding affinity of azobenzene-cyclized peptides.

• DOI: 10.1039/d0tb01189d
• 发表时间: 2020-08-26
• 期刊: Journal of materials chemistry. B
• 作者: Day K;Schneible JD;Young AT;Pozdin VA;Van Den Driessche G;Gaffney LA;Prodromou R;Freytes DO;Fourches D;Daniele M;Menegatti S
• 通讯作者: Menegatti S

Engineering Next Generation Cyclized Peptide Ligands for Light‐Controlled Capture and Release of Therapeutic Proteins

• DOI: 10.1002/adfm.202101410
• 发表时间: 2021-05
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: R. Prodromou;Kevin N. Day;Sahand Saberi-Bosari;John D Schneible;Matthew D. Mabe;A. San Miguel;M. Daniele;V. Pozdin;S. Menegatti

Towards continuous mAb purification: Clearance of host cell proteins from CHO cell culture harvests via “flow‐through affinity chromatography” using peptide‐based adsorbents

实现连续 mAb 纯化：使用基于肽的吸附剂，通过“流动”和“亲和层析”从 CHO 细胞培养物收获物中清除宿主细胞蛋白

• DOI: 10.1002/bit.28096
• 发表时间: 2022
• 期刊: Biotechnology and Bioengineering
• 影响因子: 3.8
• 作者: Sripada, Sobhana Alekhya;Chu, Wenning;Williams, Taufika Islam;Teten, Matthew A.;Mosley, Brian J.;Carbonell, Ruben G.;Lenhoff, Abraham M.;Cramer, Steven M.;Bill, Jerome;Yigzaw, Yinges
• 通讯作者: Yigzaw, Yinges

Molecular Engineering of Cyclic Azobenzene‐Peptide Hybrid Ligands for the Purification of Human Blood Factor VIII via Photo‐Affinity Chromatography

通过光亲和色谱法纯化人血液因子 VIII 的环状偶氮苯肽杂化配体的分子工程

• DOI: 10.1002/adfm.202213881
• 发表时间: 2023
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: Prodromou, Raphael;Moore, Brandyn David;Chu, Wenning;Deal, Halston;San Miguel, Adriana;Brown, Ashley Carson;Daniele, Michael Angelo‐Anthony;Pozdin, Vladimir Aleksandrovich;Menegatti, Stefano
• 通讯作者: Menegatti, Stefano

Affordable Microfluidic Bead-Sorting Platform for Automated Selection of Porous Particles Functionalized with Bioactive Compounds

经济实惠的微流珠分选平台，用于自动选择生物活性化合物功能化的多孔颗粒

• DOI: 10.1038/s41598-019-42869-5
• 发表时间: 2019
• 期刊: Scientific Reports
• 影响因子: 4.6
• 作者: Saberi-Bosari, Sahand;Omary, Mohammad;Lavoie, Ashton;Prodromou, Raphael;Day, Kevin;Menegatti, Stefano;San-Miguel, Adriana
• 通讯作者: San-Miguel, Adriana