摘要
目前,生物正交荧光探针正逐步发展为一种活细胞荧光成像的理想工具。在四嗪生物正交荧光增强型探针中,四嗪扮演着生物正交反应单元及荧光淬灭单元的双重角色,该类探针荧光的"关闭"与"开启"主要通过逆电子需求的Diels-Alder(IEDDA)生物正交反应实现。因此,为实现荧光成像的高信噪比及高特异性,本文探索设计并合成了一系列具有电子给体—π共轭—电子受体(D-π-A)结构的"开-关"型四嗪荧光探针,该系列探针与亲二烯体环辛炔发生IEDDA生物正交反应,原位生成的哒嗪结构可以充当电子受体,从而产生新的具有D-π-A效应的荧光染料,开启分子内电荷转移(intramolecular charge transfer,ICT)效应。通过调节给电子基团类型及共轭程度,实现了400~647 nm的荧光调控及高达500倍的荧光开启。本文的研究成果为四嗪生物正交荧光探针的进一步优化及其在分子影像和生物医学领域的应用奠定了基础。
Bioorthogonal fluorogenic probes are becoming an ideal tool for live-cell fluorescence imaging.With the tetrazine bioorthogonal fluorogenic probe that displays fluorescence enhancement,the tetrazine plays the dual-role of a bioorthogonal reaction unit and the fluorescence quenching unit.The"off"and"on"states of the fluorescence probe are mainly controlled through inverse electron demand Diels-Alder(IEDDA)bioorthogonal reaction.We designed a series of turn-on tetrazine fluorescent probes with Donor-π-Acceptor(D-π-A)structure to achieve a high signal-to-noise ratio and specificity of fluorescence imaging.This series of probes reacted with the dienophile bicyclononyne,and then generated pyridazine structure in-situ that acted as an electron acceptor,resulting in a new D-π-A effect of fluorescent dyes,turning on the intramolecular charge transfer(ICT)effect.By adjusting the electron-donating groups and the degree of conjugation,tunable fluorescence spectra between 400-647 nm with fluorescence turn-on enhanced up to 500-fold have been achieved.This research lays the foundation for the further optimization of tetrazine bioorthogonal fluorescent probes and their applications in molecular imaging and biomedical fields.
作者
粟敦妍
李杰
潘立立
吴昊星
毛梧宇
SU Dun-yan;LI Jie;PAN Li-li;WU Hao-xing;MAO Wu-yu(Department of Nuclear Medicine,West China Hospital,Sichuan University,Chengdu 610041,China;Sichuan Polytechnic Technician College,Chengdu 611130,China)
出处
《药学学报》
CAS
CSCD
北大核心
2021年第4期1086-1095,共10页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(21807075)
中国博士后科学基金(2018M643464)
四川大学华西医院学科卓越发展1·3·5工程项目(ZYYC08004)。
