Glutathione and Caspase-3 Responsive Cyclic Peptide Fluorescent Probes

Shi-ying Li; Hong Cheng; Bo-ru Xie; Chu-xin Li; Hao-ran Zheng; Ren-xi Zhuo; Xian-zheng Zhang

doi:10.11777/j.issn1000-3304.2017.17038

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Glutathione and Caspase-3 Responsive Cyclic Peptide Fluorescent Probes

Research Article | 更新时间：2021-01-26

- Glutathione and Caspase-3 Responsive Cyclic Peptide Fluorescent Probes
- Acta Polymerica Sinica Issue 7, Pages: 1191-1199(2017)
- 作者机构：
  
  生物医用高分子材料教育部重点实验室武汉大学化学与分子科学学院武汉 430072
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2017.17038
  CLC：
- Published：2017-7，
  
  Received：8 March 2017，
  
  Revised：3 April 2017，
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Shi-ying Li, Hong Cheng, Bo-ru Xie, Chu-xin Li, Hao-ran Zheng, Ren-xi Zhuo, Xian-zheng Zhang. Glutathione and Caspase-3 Responsive Cyclic Peptide Fluorescent Probes. [J]. Acta Polymerica Sinica (7):1191-1199(2017)
DOI：

Shi-ying Li, Hong Cheng, Bo-ru Xie, Chu-xin Li, Hao-ran Zheng, Ren-xi Zhuo, Xian-zheng Zhang. Glutathione and Caspase-3 Responsive Cyclic Peptide Fluorescent Probes. [J]. Acta Polymerica Sinica (7):1191-1199(2017) DOI： 10.11777/j.issn1000-3304.2017.17038.

摘要

设计、合成了一类新型谷胱甘肽（glutathione，GSH）和凋亡酶-3（Caspase-3）响应的环肽分子荧光探针.该类探针主要由能量共振转移（FRET）分子荧光对、Caspase-3特异性识别多肽序列和GSH响应双硫键组成，分为不含穿膜肽序列（CP）和包含穿膜肽序列（cpCP）的两种不同环肽分子荧光探针.2种环肽分子荧光探针均能实现在GSH和Caspase-3同时存在情况下的精确成像，同时具有良好的响应性、特异性和高信噪比.该类环肽分子荧光探针在细胞培养环境中具有良好的稳定性和生物相容性.利用该探针，可以实现对星形孢菌素（STS）诱发的细胞凋亡进行实时、原位的成像监测，并对抗肿瘤药物阿霉素（DOX）和顺铂（cisplatin）诱导的细胞凋亡进行成像.这种具有多重响应并能用于精确成像的分子荧光探针将极大地促进疾病的精确诊断.

Abstract

Here

we reported two cyclic peptide fluorescent probes for simultaneous glutathione (GSH) and Caspase-3 imaging. The cyclic peptide fluorescent probes were composed of 5(6)-carboxylfluorescein (FAM)/4-(dimethylaminoazo)benzene-4-carboxylic acid (dabcyl) fluorescence resonance energy transfer (FRET) pair

Caspase-3 specific peptide sequence Asp-Glu-Val-Asp (DEVD)

glutathione (GSH) responsive disulfide bond

with Arg-Arg-Arg-Arg (RRRR) cell penetration peptide unit (short as cpCP) or without cell penetration peptide (short as CP). Due to the FRET effect between FAM and Dabcyl in CP and cpCP

the FAM fluorescence was quenched with high efficiency. GSH could cleave the disulfide bond in the probes

but it would not terminate the intracellular FRET effect. And then

Caspase-3 would further recognise and cleave the DEVD peptide sequence

which would terminate the FRET process and subsequently induce dramatically fluorescence enhancement. The fluorescence recovery of the cyclic fluorescent probe was studied with or without the presence of GSH and/or Caspase-3. The fluorescent probe exhibited good stability in cell culture medium including DMEM

MEM

RMPI1640 and trypsin. And also

the cell cytotoxicity of CP and cpCP was measured against Hela cells using MTT assay. Benefitting from the RRRR cell penetration peptide sequence

cpCP could efficiently penetrate into cells. Using staurosporine (STS) as the cell apoptosis inducer

the Caspase-3 related cell apoptosis could be observed and the real time cell apoptosis was monitored

in situ

using the fluorescence recovery of cpCP. And also

doxorubicin (DOX) and cisplatin induced cell apoptosis could be monitored using cpCP as the reporter

which indicated that cpCP could be used as a tool for therapeutic efficacy evaluation. This dual-locked fluorescent probe design could extensively improve the precision for disease diagnose. Moreover

this type of cyclic peptide fluorescent probe is a versatile platform for multi-analyte imaging just by changing the response unit

which would faciliate the development of more sophisticated fluorescent probes for biological applications in the near future.

关键词

荧光探针环肽能量共振转移精确诊断

Keywords

Fluorescent probeCyclic peptideFRETPrecise diagnosis

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