A photocontrolled β-hairpin peptide
A photocontrolled β-hairpin peptide
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DOI：
10.1002/chem.200500986
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发表时间：
2006-01-23
影响因子：
4.3
通讯作者：
Renner, C
中科院分区：
文献类型：
--
作者：
Dong, SL;Löweneck, M;Renner, C
P-发夹构成肽和蛋白质中最小的P型结构。因此，基于色氨酸拉链基序的高度稳定的单体 P-发夹的开发取得了巨大的成功 [A.G. Cochran，N.J. Skelton，M.A. Starovasnik，Proc。国家。阿卡德。美国科学 2001, 98, 5578-5583]。我们已经能够基于该主题设计、合成和表征发夹，该发夹结合了基于偶氮苯的光开关，允许以前所未有的时间分辨率对β结构进行时间分辨折叠研究。在室温下，反式偶氮异构体表现出大部分无序结构；然而，光诱导异构化为顺式偶氮形式导致两个肽部分主要延伸且平行的构象，这两个肽部分通过新型光开关[3-(3-氨基甲基)苯基偶氮]苯乙酸(AMPP)连接。虽然在原始序列中，二肽 Asn-Gly 形成连接发夹两条链的 I' 型 β 转角，但这一作用由我们的光响应性 β 发夹中的 AMPP 发色团承担，显然可以充当 β I' 转角模拟物。 β-发夹结构通过核磁共振波谱测定和证实，但折叠过程可以通过 CD、IR 和荧光光谱的显着变化来监测。最后，通过化学连接将结构和功能上重要的β-发夹基序掺入蛋白质中可能允许对蛋白质结构和/或功能进行光控制。
P-Hairpins constitute the smallest P-type structures in peptides and proteins. The development of highly stable, yet monomeric P-hairpins based on the tryptophan zipper motif was therefore a remarkable success [A.G. Cochran, N.J. Skelton, M.A. Starovasnik, Proc. Natl. Acad. Sci USA 2001, 98, 5578-5583]. We have been able to design, synthesize and characterize a hairpin based on this motif which incorporates an azobenzene-based photoswitch, that allows for time-resolved folding studies of beta-structures with unprecedented time resolution. At room temperature the trans-azo isomer exhibits a mostly disordered structure; however, light-induced isomerization to the cis-azo form leads to a predominantly extended and parallel conformation of the two peptide parts, which are linked by the novel photoswitch, [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP). While in the original sequence the dipeptide Asn-Gly forms a type I' beta-turn which connects the two strands of the hairpin, this role is adopted by the AMPP chromophore in our photoresponsive beta-hairpin that can apparently act as a beta I'-turn mimetic. The beta-hairpin structure was determined and confirmed by NMR spectroscopy, but the folding process can be monitored by pronounced changes in the CD, IR and fluorescence spectra. Finally, incorporation of the structurally and functionally important beta-hairpin motif into proteins by chemical ligation might allow for the photocontrol of protein structures and/or functions.