PMID- 37876282
OWN - NLM
STAT- MEDLINE
DCOM- 20231122
LR  - 20231122
IS  - 1364-5528 (Electronic)
IS  - 0003-2654 (Linking)
VI  - 148
IP  - 23
DP  - 2023 Nov 20
TI  - Substituted kynurenic acid derivatives as fluorophore-based probes for D- and 
      L-amino acid oxidase assays and their in vitro application in eels.
PG  - 5991-6000
LID - 10.1039/d3an01325a [doi]
AB  - High levels of D-amino acid oxidase (DAO) are associated with neurological and 
      psychiatric disorders, while L-amino acid oxidase (LAO) exhibits antimicrobial 
      and antitumor properties. The enzymatic conversion of the non-fluorescent 
      kynurenine (KYN) into the endogenous weak fluorescent kynurenic acid (KYNA) by 
      the action of DAO has previously been reported. However, the fluorescence of KYNA 
      can be improved by changing the substituents on the aromatic rings. In this 
      study, we prepared different 6-phenyl-substituted KYNA derivatives and 
      investigated their fluorescence properties. Among them, 2-MePh-KYNA showed the 
      maximum fluorescence quantum yield of 0.881 at 340 nm excitation and 418 nm 
      emission wavelengths. The effects of solvent properties (dielectric constant, 
      pK(a), viscosity, and proticity) on the fluorescence intensity (FLI) of the KYNA 
      derivatives were explored. The FLI of 2-MePh-KYNA was significantly large in 
      protic solvents. Subsequently, 2-MePh-D-KYN and 2-MePh-L-KYN were prepared with 
      high enantiopurity (>99.25%) for the enzymatic conversion. 2-MePh-D-KYN exhibited 
      high sensitivity ( approximately 19 times that of a commercial DAO substrate and  approximately 60 times that 
      of the previously reported MeS-D-KYN) and high selectivity, as it was not 
      cross-reactive towards LAO, while 2-MePh-L-KYN was also converted into 
      2-MePh-KYNA by LAO. Furthermore, the 2-MePh-D-KYN probe successfully detected DAO 
      in eel liver, kidney, and heparin-anticoagulated plasma in the in vitro study.
FAU - Sakamoto, Tatsuya
AU  - Sakamoto T
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan. 
      t-fukushima@phar.toho-u.ac.jp.
FAU - Onozato, Mayu
AU  - Onozato M
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan. 
      t-fukushima@phar.toho-u.ac.jp.
FAU - Sugasawa, Hiroshi
AU  - Sugasawa H
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan. 
      t-fukushima@phar.toho-u.ac.jp.
FAU - Fukushima, Takeshi
AU  - Fukushima T
AUID- ORCID: 0000-0002-6086-4156
AD  - Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan. 
      t-fukushima@phar.toho-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20231120
PL  - England
TA  - Analyst
JT  - The Analyst
JID - 0372652
RN  - H030S2S85J (Kynurenic Acid)
RN  - 0 (Fluorescent Dyes)
RN  - EC 1.4.3.2 (L-Amino Acid Oxidase)
RN  - EC 1.4.3.3 (D-Amino-Acid Oxidase)
SB  - IM
MH  - *Kynurenic Acid/chemistry
MH  - Fluorescent Dyes
MH  - Eels
MH  - Animals
MH  - *L-Amino Acid Oxidase/analysis
MH  - *D-Amino-Acid Oxidase/analysis
MH  - Biological Assay
MH  - Fluorescence
MH  - Kinetics
MH  - Liver/enzymology
MH  - Kidney/enzymology
EDAT- 2023/10/25 06:42
MHDA- 2023/11/21 06:42
CRDT- 2023/10/25 03:43
PHST- 2023/11/21 06:42 [medline]
PHST- 2023/10/25 06:42 [pubmed]
PHST- 2023/10/25 03:43 [entrez]
AID - 10.1039/d3an01325a [doi]
PST - epublish
SO  - Analyst. 2023 Nov 20;148(23):5991-6000. doi: 10.1039/d3an01325a.