四嗪生物正交点击-释放反应释放多肽研究与应用

Tetrazine bioorthogonal click-to-release reaction for releasing peptides

本文探索了四嗪生物正交点击-释放反应对多肽化合物的碳端释放效率,并尝试了其在固相合成中对多肽进行功能化修饰及温和切除上的应用。设计合成了13个反式环辛烯多肽衍生物,与四嗪发生生物正交反应后,多肽1 h释放率为90.0%~97.7%。该策略对多肽侧链官能团及肽链长度具有良好兼容性,扩大了四嗪生物正交点击-释放反应的应用范围。同时,设计合成新颖的双功能化反式环辛烯分子,在固相树脂上实现了对活性肽GIRLRG的荧光修饰,并利用四嗪点击-释放反应温和切除,为多肽的固相修饰、释放策略提供了新思路。

This paper aimed to investigate the release efficiency of peptide at carbon terminal triggered by tetrazine bioorthogonal click-to-release reaction,and further explored the potential application of this reaction in functional modification and mild cleavage in solid-phase peptide synthesis.Thirteen peptide derivatives modified by trans-cyclooctene(TCO)were designed and synthesized,which were reacted with tetrazine to release the peptides.The results showed that the release rates of peptide were 90.0%to 97.7%in one hour.The strategy has good compatibility with the functional side-groups and the length of peptides,which expands the applications scope of tetrazine bioorthogonal click-to-release reaction.At the same time,a novel bifunctional trans-cyclooctene molecule was designed and synthesized.The active peptide GIRLRG was modified by fluorophore on the solidphase resin,and released through tetrazine click-to-release reaction under mild condition,providing a new strategy for the solid-phase modification and release strategy of the peptide.