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通过光动力调节膜流动性和整合来控制合成转运蛋白的活性。

Activity Control of a Synthetic Transporter by Photodynamic Modulation of Membrane Mobility and Incorporation.

机构信息

Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.

Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, United States.

出版信息

J Am Chem Soc. 2024 Nov 13;146(45):31085-31093. doi: 10.1021/jacs.4c10952. Epub 2024 Nov 1.

Abstract

Artificial transmembrane transport systems are receiving a great deal of attention for their potential therapeutic application. A major challenge is to switch their activity in response to environmental stimuli, which has been achieved mostly by modulating the binding affinity. We demonstrate here that the activity of a synthetic anion transporter can be controlled through changes in the membrane mobility and incorporation. The transporters─equipped with azobenzene photoswitches─poorly incorporate into the bilayer membrane as their thermally stable (,,)-isomers, but incorporation is triggered by UV irradiation to give the ()-containing isomers. The latter isomers, however, are found to have a lower mobility and are therefore the least active transporters. This opposite effect of - isomerization on transport capability offers unique photocontrol as is demonstrated by irradiation studies during the used transport assays. These results help to understand the behavior of artificial transporters in a bilayer and are highly important to future designs, with new modes of biological activity and with the possibility to direct motion, which may be crucial toward achieving active transport.

摘要

人工跨膜转运系统因其潜在的治疗应用而受到广泛关注。一个主要的挑战是通过调节结合亲和力来响应环境刺激来切换其活性。我们在这里证明,通过改变膜流动性和掺入,合成阴离子转运体的活性可以得到控制。这些转运体配备有偶氮苯光开关,当它们处于热稳定的(,)-异构体时,很难掺入双层膜中,但通过紫外线照射可以触发含有()的异构体掺入。然而,后一种异构体的流动性较低,因此是最不活跃的转运体。这种异构化对转运能力的相反影响提供了独特的光控,这在用于转运测定的 照射研究中得到了证明。这些结果有助于理解人工转运体在双层中的行为,对于未来的设计非常重要,具有新的生物活性模式和引导运动的可能性,这对于实现主动转运可能至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b63/11565646/8f6d0a2c807f/ja4c10952_0007.jpg

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