RUI: Protein Bioconjugation Strategies for Next Generation Silk Biomaterials

RUI：下一代丝生物材料的蛋白质生物共轭策略

• 批准号: 1807878
• 负责人: Amanda Murphy
• 金额: $ 38.89万
• 依托单位: Western Washington University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807878&HistoricalAwards=false
• 关键词: RUI; Protein; Bioconjugation; Strategies; Next

Non-technical Abstract:Bombyx mori silkworms produce cocoons made of a fascinating protein called silk fibroin. In recent years, silk has become one of the most popular biomedical materials for applications ranging from drug delivery to creating artificial tissues. Successful development of the protein modification strategies described here will pave the way for researchers to design the next generation of innovative, functional silk-based biomaterials with enhanced performance and integration with biological systems. In the Department of Chemistry at Western Washington University, our core mission is to provide undergraduate students with significant, in-depth research opportunities. The proposed research program will involve a total of ~10-12 undergraduates and 2-3 master?s students over the three-year grant period. Recognizing that community colleges offer critical access to higher education for many underrepresented groups, this grant will provide one additional research stipend per summer for a local community college student. Overall, this work will give students a strong foundation in the skills required to be successful in STEM-related careers, will foster further collaborations between faculty both within and outside of WWU, and will continue to build relationships between WWU and local community colleges. Technical Abstract: Silk produced by the Bombyx mori silkworm has emerged as one of the most versatile biomaterials for applications ranging from engineered tissues, to drug delivery, to optical and electronic devices. Chemical modification of the silk protein provides an opportunity to further customize the interaction between silk and living systems, and endow silk with new functionality. Given the limitations in selectivity and functional group tolerance of previously employed bioconjugation methods, there is a need for complementary chemistries for silk modification, particularly bio-orthogonal reactions that occur under mild, aqueous conditions. To this end, the primary goal of this work is to develop new methods to chemically-modify the unusually high number of tyrosine residues in silk by employing 1) amino tyrosine modification strategies and 2) palladium-catalyzed cross-coupling reactions. While the methods developed here can be broadly applied, we will focus on silk derivatives that will be valuable for in vitro and in vivo imaging applications and targeted drug delivery. Overall, this work involves fundamental explorations of silk protein reactivity, furthers efforts to translate traditional organic reactions into aqueous environments, and ultimately will result in new protein bioconjugation methods that can be applied to silk and other tyrosine-containing proteins.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.

非技术摘要：家蚕生产的茧是由一种叫做丝素蛋白的迷人蛋白质制成的。近年来，丝绸已成为最受欢迎的生物医学材料之一，其应用范围从药物输送到制造人造组织。这里描述的蛋白质修饰策略的成功开发将为研究人员设计下一代创新的功能性丝基生物材料铺平道路，该材料具有增强的性能并与生物系统集成。在西华盛顿大学化学系，我们的核心使命是为本科生提供重要、深入的研究机会。拟议的研究计划将在三年资助期内总共涉及约 10-12 名本科生和 2-3 名硕士生。认识到社区大学为许多代表性不足的群体提供了接受高等教育的重要机会，这笔赠款将为当地社区学院的学生每年夏天提供一份额外的研究津贴。总体而言，这项工作将为学生在 STEM 相关职业中取得成功所需的技能奠定坚实的基础，将促进 WWU 内外教师之间的进一步合作，并将继续建立 WWU 与当地社区学院之间的关系。技术摘要：由家蚕生产的丝已成为最通用的生物材料之一，其应用范围包括工程组织、药物输送、光学和电子设备。丝蛋白的化学修饰为进一步定制丝与生命系统之间的相互作用提供了机会，并赋予丝新的功能。鉴于先前采用的生物共轭方法在选择性和官能团耐受性方面的局限性，需要用于丝修饰的补充化学物质，特别是在温和的水性条件下发生的生物正交反应。为此，这项工作的主要目标是开发新方法，通过采用 1) 氨基酪氨酸修饰策略和 2) 钯催化的交叉偶联反应，对丝绸中异常大量的酪氨酸残基进行化学修饰。虽然这里开发的方法可以广泛应用，但我们将重点关注对体外和体内成像应用以及靶向药物输送有价值的丝衍生物。总体而言，这项工作涉及对丝蛋白反应性的基础探索，进一步努力将传统的有机反应转化为水性环境，最终将产生可应用于丝和其他含酪氨酸蛋白的新的蛋白质生物共轭方法。该奖项反映了 NSF 的法定使命，并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，被认为值得支持。

项目成果

Synthesis and Characterization of Highly Thiolated Silk Fibroin

高硫醇化丝素蛋白的合成与表征

• DOI: 10.1002/macp.202300340
• 发表时间: 2023
• 期刊: Macromolecular Chemistry and Physics
• 影响因子: 2.5
• 作者: Talusig, Jeremy M.;Murphy, Amanda R.
• 通讯作者: Murphy, Amanda R.

Chemical Modification of Silk Proteins via Palladium‐Mediated Suzuki−Miyaura Reactions

通过钯介导的铃木反应对丝蛋白进行化学修饰

• DOI: 10.1002/macp.202300307
• 发表时间: 2023
• 期刊: Macromolecular Chemistry and Physics
• 影响因子: 2.5
• 作者: Santen, Racine M.;Owens, Kayla M.;Echague, Keith C.;Murphy, Amanda R.
• 通讯作者: Murphy, Amanda R.