Tuning the affinity of probes with transmembrane proteins by constructing peptide-conjugated cis/trans isomers based on molecular scaffolds†

IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Jing-Jing Hu, Juliang Yang, Yiheng Liu, Guangwen Lu, Zujin Zhao, Fan Xia and Xiaoding Lou
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Abstract

For protein analysis, the current peptide-based probes rely almost on the specific recognition of the protein while neglecting the potential influence of the environment near the protein. Herein, we propose that to achieve high recognition of transmembrane protein integrin αvβ3, the interactions from the membrane substrate could be helpful. Moreover, to guarantee the additive effect of different interactions, the cis and trans isomers of peptide-based probes are distinguished. In detail, we synthesized the peptide-conjugated cis/trans isomers (cis-RTP and trans-RTP) by modifying the Arg-Gly-Asp (RGD)-targeting peptide and palmitic acid-conjugated Arg-Arg-Arg-Arg (Pal-RRRR) peptide to the two ends of the molecular scaffold-tetraphenylethene derivative. Due to the difference in spatial structure, isothermal titration calorimetry and simulation experiments demonstrated that cis-RTP can bind more stably to integrin αvβ3 than trans-RTP. As a result, cis-RTP has shown more excellent properties in inhibiting cell migration and killing cells by regulating actin and extracellular signal-regulated kinase. Unlike the existing probe design for protein, this study provides a concept of microenvironment-helpful recognition and a promising strategy of cis/trans isomers to modulate the interaction between proteins and probes.

Abstract Image

通过构建基于分子支架的肽结合顺/反异构体,调整探针与跨膜蛋白的亲和力。
在蛋白质分析中,目前基于多肽的探针几乎依赖于对蛋白质的特异性识别,而忽略了蛋白质附近环境的潜在影响。在此,我们提出,要实现对跨膜蛋白整合素αvβ3的高识别率,膜底物的相互作用会有所帮助。此外,为了保证不同相互作用的相加效应,我们还区分了多肽探针的顺式和反式异构体。具体来说,我们将Arg-Gly-Asp(RGD)靶向肽和棕榈酸共轭Arg-Arg-Arg-Arg(Pal-RRR)肽修饰到分子支架-四苯基乙烯衍生物的两端,合成了肽共轭顺式/反式异构体(顺式-RTP和反式-RTP)。由于空间结构的不同,等温滴定量热法和模拟实验证明,顺式-RTP 比反式-RTP 能更稳定地与整合素 αvβ3 结合。因此,顺式-RTP 在通过调节肌动蛋白和细胞外信号调节激酶来抑制细胞迁移和杀死细胞方面表现出更优异的性能。与现有的蛋白质探针设计不同,这项研究提供了一种微环境辅助识别的概念,以及一种顺式/反式异构体调节蛋白质与探针之间相互作用的可行策略。
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来源期刊
Journal of Materials Chemistry B
Journal of Materials Chemistry B MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.30%
发文量
866
期刊介绍: Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive: Antifouling coatings Biocompatible materials Bioelectronics Bioimaging Biomimetics Biomineralisation Bionics Biosensors Diagnostics Drug delivery Gene delivery Immunobiology Nanomedicine Regenerative medicine & Tissue engineering Scaffolds Soft robotics Stem cells Therapeutic devices
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