Huang Yun, Cong Zhiyuan, Yang Longfei, Dong Shouliang
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China.
J Pept Sci. 2008 Sep;14(9):1062-8. doi: 10.1002/psc.1042.
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)-Tyr(2)-psi[CS-N]-Pro(3)-Trp(4)-Gly(5)-NH(2) (psiCS-N-kinin), was synthesized by Fmoc solid-phase peptide strategy. The reversible photoswitching 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 UV 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 psiCS-N-kinin conformer is the active conformation when interacting with kinin receptor on cockroach hindgut.
硫代肽键psi[CS-N]是天然肽键的一种近乎等电子体修饰，被引入昆虫激肽活性核心五肽中，以评估主链顺式/反式光开关对生物活性的影响。硫代类似物Phe(1)-Tyr(2)-psi[CS-N]-Pro(3)-Trp(4)-Gly(5)-NH(2)（psiCS-N-激肽）通过Fmoc固相肽策略合成。通过光谱方法和高效液相色谱对可逆光开关特性进行了表征，结果表明，在254nm紫外线照射后，顺式构象异构体从15.7%增加到47.7%。缓慢的热异构化（t(1/2)=40分钟）使我们能够确定硫代肽在光稳态下对蟑螂后肠的肌otropic活性。结果表明，紫外线照射后活性显著增加，热再平衡后恢复到基线水平。在本研究中，通过利用肽主链特定位置的光触发异构化，我们揭示了顺式psiCS-N-激肽构象异构体在与蟑螂后肠激肽受体相互作用时是活性构象。
