Discovery of Turn-On Fluorescent Probes for Detecting PDEδ Protein in Living Cells and Tumor Slices

Gaopan Dong; Long Chen; Jing Zhang; Tingting Liu; Lupei Du; Chunquan Sheng; Minyong Li

doi:10.1021/acs.analchem.0c00335

Discovery of Turn-On Fluorescent Probes for Detecting PDEδ Protein in Living Cells and Tumor Slices

Anal Chem. 2020 Jul 21;92(14):9516-9522. doi: 10.1021/acs.analchem.0c00335. Epub 2020 Jul 9.

Authors

Gaopan Dong¹, Long Chen², Jing Zhang³, Tingting Liu^{1

4}, Lupei Du¹, Chunquan Sheng², Minyong Li¹

Affiliations

¹ Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
² Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
³ Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
⁴ Institute of Pharmacology, School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 271000, China.

PMID: 32571022
DOI: 10.1021/acs.analchem.0c00335

Abstract

The first small-molecule fluorescent turn-on probes for detecting PDEδ protein were rationally designed, showing reasonable fluorescent properties and the fluorescent ability has been applied for visualization of the PDEδ protein in living cells and at tissue levels. The qPCR results showed that the mRNA expression of KRAS, PDEδ, AKT1, MAPK1, MEK7, RAF1, and mTOR were downregulated by probes 1-3 through PI3K/AKT/mTOR and MAPK signal pathways. The probes also can downregulate the protein level of pErk and tErk. Therefore, these small-molecule fluorescent probes are expected to be used in the screening of antipancreatic cancer drugs targeting the PDEδ protein, as well as in obtaining a better understanding of the pathological and physiological roles of PDEδ protein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Catalytic Domain
Cell Survival / drug effects
Fluorescent Dyes / chemistry*
Gene Expression Regulation, Enzymologic / physiology*
Gene Expression Regulation, Neoplastic / physiology*
Humans
MAP Kinase Kinase 7 / genetics
MAP Kinase Kinase 7 / metabolism
Mice
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / metabolism
Molecular Structure
Neoplasms / enzymology*
Phosphoric Diester Hydrolases / chemistry
Phosphoric Diester Hydrolases / metabolism*
Protein Conformation
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-raf / genetics
Proto-Oncogene Proteins c-raf / metabolism
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / metabolism
Skin / enzymology
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism

Substances

Biomarkers
Fluorescent Dyes
KRAS protein, human
MTOR protein, human
AKT1 protein, human
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-raf
Raf1 protein, human
TOR Serine-Threonine Kinases
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
MAP Kinase Kinase 7
MAP2K7 protein, human
Phosphoric Diester Hydrolases
Proto-Oncogene Proteins p21(ras)