以D-π-A为基本骨架的用于脑内Aβ斑块检测的近红外探针的研究
详细信息 查看官网全文
- 英文论文题名：D-π-A architecture based near-infrared probes targeted Aβ plaques in the brain
- 论文作者：周凯翔 ; 付化龙 ; 崔孟超
- 英文论文作者：Kaixiang Zhou ; Hualong Fu ; Mengchao Cui ; Department of Chemistry ; University of Beijing Normal University
- 年：2016
- 作者机构：北京师范大学化学学院放射性药物教育部重点实验室;
- 论文关键词：Aβ斑块 ; 近红外探针 ; D-π-A ; 荧光染色 ; 活体成像
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：R446.1;O657.33
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：279k
- 原文格式：D
- 会议级别：全国
摘要
D-π-A骨架对于设计以Ab斑块为靶点的近红外探针具有重要意义[1]。因此,我们继续深入的设计并合成了21个以D-π-A骨架为基本结构的近红外探针,系统详细的研究了不同电子供体以及共轭π键的长度对于探针的荧光性质以及生物性质的影响。并且筛选出性质最为良好的两个探针进行了活体内的荧光成像以及体内染色。首先,我们测定了化合物的荧光性质包括紫外吸收值,最大荧光发射波长,绝对量子产率,而这些数据与电子供体提供电子的能力以及共轭双键数目有重要联系,并且证明探针对于溶剂极性非常敏感。体外竞争结合实验数据以及2分钟的初始脑摄取量表明一定共轭双键数目的(n=3,4,5)探针与Ab_(1-42)聚集体均具有高的亲和力以及优良的透过血脑屏障的能力。活体近红外成像显示PHC-4和PYC-4能有效穿过血脑屏障,具有较快的脑清除速率,而且能有效地区分AD转基因小鼠与正常小鼠。因此,具有潜在的临床应用前景。
D-π-A structure is crucial even necessary for researchers to design high affinity and excellent optical properties NIRF probes targeted Aβ plaques.Herein,three series of compounds were designed and synthesized,we made it that extending the double bonds from one to seven and changing the donor ring from phenyl ring to pyridine ring or pyrimidine ring.In this study,we systematically revealed that optical properties(emission wavelength,fluorescence intensity,ultraviolet spectrum),brain uptake,binding affinity were highly associated with the structure characteristics(donor rings,the length of double bonds),and these intriguing structure-activity relationships(SARs)have been discussed in detail.
D-π-A structure is crucial even necessary for researchers to design high affinity and excellent optical properties NIRF probes targeted Aβ plaques.Herein,three series of compounds were designed and synthesized,we made it that extending the double bonds from one to seven and changing the donor ring from phenyl ring to pyridine ring or pyrimidine ring.In this study,we systematically revealed that optical properties(emission wavelength,fluorescence intensity,ultraviolet spectrum),brain uptake,binding affinity were highly associated with the structure characteristics(donor rings,the length of double bonds),and these intriguing structure-activity relationships(SARs)have been discussed in detail.
引文
[1]Mengchao Cui.et al.Journal of America Society.2014,136,3388-3394