Title:
AGGREGATION-INDUCED EMISSION PRINCIPLE-BASED AUTOPHAGY DETECTION MOLECULAR PROBE AND MANUFACTURING METHOD THEREFOR AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/082185
Kind Code:
A1
Abstract:
The present invention relates to the field of molecular probes, specifically to an aggregation-induced emission principle-based autophagy detection molecular probe. The structure of the probe sequentially comprises an LC3 protein targeting peptide capable of targeting LC3 molecules, a cell penetrating peptide capable of improving the water solubility of the whole probe and promoting the probe to enter cells, and aggregation-induced emission tetraphenyl ethylene capable of emitting fluorescence when the binding movement with LC3 is limited. The molecule probe of the present invention has the characteristics of cellular internalization, specific interaction with LC3, aggregation-induced emission, being non-cytotoxic, not leading autophagy effect by itself, etc.; the difference of the autophagy intensity of cells can be visually observed under an optical microscope; the difference of the autophagy intensity of the cells can be analyzed and monitored by means of flow cytometry; a cell subpopulation with different autophagy levels can be separated from normally cultured cells or a primary cell population; and the general heterogeneity of basic autophagy levels in various cell types is disclosed. The present invention further provides a manufacturing method for and application of the molecule probe.
Inventors:
WEN LONGPING (CN)
ZHANG YUNJIAO (CN)
WEI PENGFEI (CN)
ZHANG WENBIN (CN)
LIU LIU (CN)
ZHANG YUNJIAO (CN)
WEI PENGFEI (CN)
ZHANG WENBIN (CN)
LIU LIU (CN)
Application Number:
PCT/CN2021/130368
Publication Date:
May 19, 2023
Filing Date:
November 12, 2021
Export Citation:
Assignee:
UNIV SOUTH CHINA TECH (CN)
International Classes:
C07K7/06; C09K11/06
Domestic Patent References:
| WO2016165487A1 | 2016-10-20 |
Foreign References:
| CN101775072A | 2010-07-14 | |||
| CN106267243A | 2017-01-04 | |||
| CN106470964A | 2017-03-01 |
Other References:
"Doctoral Dissertation", 18 May 2017, HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY, CN, article CHENG, YONG: "Synthesis and Application of Peptide-conjugated Fluorescent Probe with Aggregation-induce Emission Characteristics in Cancer Diagnosis and Treatment", pages: 1 - 195, XP009545560
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XIA FAN, WU JUN, WU XIA, HU QINYU, DAI JUN, LOU XIAODING: "Modular Design of Peptide- or DNA-Modified AIEgen Probes for Biosensing Applications", ACCOUNTS OF CHEMICAL RESEARCH, ACS , WASHINGTON , DC, US, vol. 52, no. 11, 19 November 2019 (2019-11-19), US , pages 3064 - 3074, XP093065894, ISSN: 0001-4842, DOI: 10.1021/acs.accounts.9b00348
CHENG YONG, SUN CHUNLI, OU XIAOWEN, LIU BIFENG, LOU XIAODING, XIA FAN: "Dual-targeted peptide-conjugated multifunctional fluorescent probe with AIEgen for efficient nucleus-specific imaging and long-term tracing of cancer cells", CHEMICAL SCIENCE, ROYAL SOCIETY OF CHEMISTRY, UNITED KINGDOM, vol. 8, no. 6, 1 January 2017 (2017-01-01), United Kingdom , pages 4571 - 4578, XP093065896, ISSN: 2041-6520, DOI: 10.1039/C7SC00402H
JOHANSEN TERJE ET AL.: "Selective Autophagy Mediated by Autophagic Adapter Proteins", AUTOPHAGY, vol. 7, no. 3, 1 March 2011 (2011-03-01), XP055886419, DOI: 10.4161/auto.7.3.14487
LIN XIAOLONG, LI SHUANG, ZHAO YUE, MA XIAOFENG, ZHANG KAI, HE XINGLAN, WANG ZUO: "Interaction Domains of p62: A Bridge Between p62 and Selective Autophagy", DNA AND CELL BIOLOGY, MARY ANN LIEBERT, NEW YORK, NY, US, vol. 32, no. 5, 1 May 2013 (2013-05-01), US , pages 220 - 227, XP093065901, ISSN: 1044-5498, DOI: 10.1089/dna.2012.1915
SRINIVASAN DIVYAMANI ET AL.: "Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine", PLOS ONE, vol. 6, no. 3, 14 March 2011 (2011-03-14), XP055879658, DOI: 10.1371/journal.pone.0017732
CHENG YONG, HUANG FUJIAN, MIN XUEHONG, GAO PENGCHENG, ZHANG TIANCHI, LI XINCHUN, LIU BIFENG, HONG YUNING, LOU XIAODING, XIA FAN: "Protease-Responsive Prodrug with Aggregation-Induced Emission Probe for Controlled Drug Delivery and Drug Release Tracking in Living Cells", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 88, no. 17, 6 September 2016 (2016-09-06), US , pages 8913 - 8919, XP093065890, ISSN: 0003-2700, DOI: 10.1021/acs.analchem.6b02833
XIA FAN, WU JUN, WU XIA, HU QINYU, DAI JUN, LOU XIAODING: "Modular Design of Peptide- or DNA-Modified AIEgen Probes for Biosensing Applications", ACCOUNTS OF CHEMICAL RESEARCH, ACS , WASHINGTON , DC, US, vol. 52, no. 11, 19 November 2019 (2019-11-19), US , pages 3064 - 3074, XP093065894, ISSN: 0001-4842, DOI: 10.1021/acs.accounts.9b00348
CHENG YONG, SUN CHUNLI, OU XIAOWEN, LIU BIFENG, LOU XIAODING, XIA FAN: "Dual-targeted peptide-conjugated multifunctional fluorescent probe with AIEgen for efficient nucleus-specific imaging and long-term tracing of cancer cells", CHEMICAL SCIENCE, ROYAL SOCIETY OF CHEMISTRY, UNITED KINGDOM, vol. 8, no. 6, 1 January 2017 (2017-01-01), United Kingdom , pages 4571 - 4578, XP093065896, ISSN: 2041-6520, DOI: 10.1039/C7SC00402H
JOHANSEN TERJE ET AL.: "Selective Autophagy Mediated by Autophagic Adapter Proteins", AUTOPHAGY, vol. 7, no. 3, 1 March 2011 (2011-03-01), XP055886419, DOI: 10.4161/auto.7.3.14487
LIN XIAOLONG, LI SHUANG, ZHAO YUE, MA XIAOFENG, ZHANG KAI, HE XINGLAN, WANG ZUO: "Interaction Domains of p62: A Bridge Between p62 and Selective Autophagy", DNA AND CELL BIOLOGY, MARY ANN LIEBERT, NEW YORK, NY, US, vol. 32, no. 5, 1 May 2013 (2013-05-01), US , pages 220 - 227, XP093065901, ISSN: 1044-5498, DOI: 10.1089/dna.2012.1915
SRINIVASAN DIVYAMANI ET AL.: "Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine", PLOS ONE, vol. 6, no. 3, 14 March 2011 (2011-03-14), XP055879658, DOI: 10.1371/journal.pone.0017732
Attorney, Agent or Firm:
WAYNE INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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