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Novel 19 F‐ MRS β‐galactosidase reporter molecules incorporated nitrogen mustard analogues
Author(s) -
Yu Zijun,
Zhao Jianru,
Hua Zhiming,
Wang Xinping,
Wang Xiaobo,
Wang Hanqin,
Yu JianXin
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12992
Subject(s) - chemistry , glycosylation , in vitro , hydrolysis , stereochemistry , molecule , click chemistry , biochemistry , combinatorial chemistry , organic chemistry
In this study, we propose a novel molecular platform‐integrated fluorinated antitumor nitrogen mustards for 19 F‐ MRS assay of β‐galactosidase (β‐gal) activity. Following this idea, we have designed, synthesized, and characterized 2‐fluoro‐4‐[bis(2′‐chloroethyl)amino]phenyl β‐ D ‐galactopyranoside 5 , 2‐fluoro‐4‐{bis[2′‐ O ‐(β‐ D ‐galactopyranosyl)ethyl]amino}phenyl β‐ D ‐galactopyranoside 8 , 2‐fluoro‐4‐{bis[[1″‐(β‐ D ‐galactopyranosyl)‐1″, 2″, 3″‐triazol‐4″‐yl]methyl] amino}phenyl β‐ D ‐galactopyranoside 14 and 2‐fluoro‐4‐{bis[[1″‐(β‐ D ‐glucopyranosyl)‐1″, 2″, 3″‐triazol‐4″‐yl]methyl]amino}phenyl β‐ D ‐galactopyranoside 15 through glycosylation and click reaction strategies, and their structures were confirmed by NMR and HRMS or elemental analysis data. Among them, 2‐fluoro‐4‐[bis(2′‐chloroethyl)amino]phenyl β‐ D ‐galacto‐pyranoside 5 was found very sensitive to β‐gal (E801A) in PBS at 37°C with big Δδ F response. Here, we demonstrated the feasibility of this platform for assessing β‐gal activity in solution, and in vitro with lacZ ‐transfected human MCF 7 breast and PC 3 prostate tumor cells, by the characterization of β‐gal‐responsive 19 F‐chemical shift changes Δδ F and hydrolytic kinetics.