A photoswitchable thioxopeptide bond facilitates the conformation-activity correlation study of insect kinin
A photoswitchable thioxopeptide bond facilitates the conformation-activity correlation study of insect kinin
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光开关硫代肽键促进昆虫激肽的构象-活性相关性研究
DOI：
10.1002/psc.1042
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发表时间：
2008-09-01
影响因子：
2.1
通讯作者：
Dong, Shouliang
中科院分区：
文献类型：
--
作者：
Huang, Yun;Cong, Zhiyuan;Dong, Shouliang
将硫代肽键psi[CS-N]引入到昆虫激肽活性核心五肽中，研究了骨架顺/反光开关对活性的影响。采用Fmoc固相合成法合成了硫代类似物Phe（1）-Tyr 2-psi[CS-N]-pro（3）-Trp（4）-Gly（5）-NH 2（psi[CS-N]（2）-kinin）。通过光谱法和高效液相色谱法表征了其可逆的光开关性质，结果表明，在254 nm的紫外光照射下，顺式构象异构体从15.7%增加到47.7%。一个缓慢的热重异构化（t（1/2）= 40分钟），使我们能够确定蟑螂后肠肌活性的硫代肽在光稳态。结果表明，LJV照射后，活性显著增加，热平衡后恢复到基础水平。本研究利用肽骨架上特定位置的光引发异构化，发现cis psi[CS-N]（2）-kinin构象是与蟑螂后肠激肽受体相互作用的活性构象。版权所有（c）2008欧洲肽协会和约翰威利父子有限公司。
Thioxopeptide bond psi[CS-N], a nearly isosteric modification of the native peptide bond, was introduced into insect kinin active core pentapeptide to evaluate the impact of backbone cis/trans photoswitching on bioactivity. The thioxo analog Phe(1)-Tyr2-psi[CS-N]-pro(3)-Trp(4)-Gly(5)-NH2 (psi[CS-N](2)-kinin), was synthesized by Fmoc solid-phase peptide strategy. The reversible photeswitching property was characterized via spectroscopic methods and HPLC, which showed that the cis conformer increased from 15.7 to 47.7% after 254 nm UV irradiation. A slow thermal reisomerization (t(1/2) = 40 min) permitted us to determine the cockroach hindgut myotropic activity of the thioxopeptide in the photostationary state. The results indicated that the activity increased significantly after LJV irradiation and recovered to the ground level after thermal re-equilibration. In the present study, by utilizing the phototriggered isomerization in a specific position of peptide backbone, we revealed that the cis psi[CS-N](2)-kinin conformer is the active conformation when interacting with kinin receptor on cockroach hindgut. Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.