RRC ID 57826
Author Kawatani M, Yamamoto K, Yamada D, Kamiya M, Miyakawa J, Miyama Y, Kojima R, Morikawa T, Kume H, Urano Y.
Title Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity.
Journal J Am Chem Soc
Abstract Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.
Volume 141(26)
Pages 10409-10416
Published 2019-7-3
DOI 10.1021/jacs.9b04412
PMID 31244179
MeSH Antigens, Surface / analysis Antigens, Surface / metabolism* Cell Line, Tumor Fluorescence* Fluorescent Dyes / chemistry* Glutamate Carboxypeptidase II / analysis Glutamate Carboxypeptidase II / metabolism* Humans Male Molecular Structure Optical Imaging PC-3 Cells Prostatic Neoplasms / diagnostic imaging* Prostatic Neoplasms / metabolism Recombinant Proteins / analysis Recombinant Proteins / metabolism Spectrometry, Fluorescence Substrate Specificity
IF 14.695
Times Cited 7
Human and Animal Cells LNCap.FGC(RCB2144)