PMID- 29441684
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20180904
IS  - 1097-0231 (Electronic)
IS  - 0951-4198 (Linking)
VI  - 32
IP  - 8
DP  - 2018 Apr 30
TI  - Development of drug discovery screening system by molecular interaction 
      kinetics-mass spectrometry.
PG  - 665-671
LID - 10.1002/rcm.8083 [doi]
AB  - RATIONALE: Drug discovery studies invariably require qualitative and quantitative 
      analyses of target compounds at every stage of drug discovery. We have developed 
      a system combining molecular interaction analysis and mass spectrometry (LC-MS) 
      using the principle of nanopore optical interferometry (nPOI) called molecular 
      interaction kinetics-mass spectrometry (MIK-MS). Since nPOI has high binding 
      capacity, the bond-dissociated compound can be directly detected using LC-MS. In 
      this study, we use carbonic anhydrase II (CAII) as a ligand and apply six small 
      compounds as analytes and report the affinity analysis using MIK-MS. METHODS: 
      CAII was immobilized onto a COOH sensor chip using standard amine coupling. A 
      reference surface was prepared by activating and subsequently blocking the 
      surface under identical conditions. An amount of 50 muL of mix solution was 
      injected over the reference channel and sample channel for CAII immobilization. 
      The solutions eluting from the sensor chip were collected from the waste-line of 
      the SKi Pro system every 30 s. Reconstructed elution samples were then injected 
      into the LC-MS/MS system. RESULTS: A mixture containing furosemide, 
      acetazolamide, 4-sulfamoylbenzoic acid, 5-(dimethylamino)-1-naphthalene 
      sulfonamide (DNSA), sulfanilamide and sulpiride (15 muM each) was injected into 
      the CAII-immobilized sensor chip, and the fractions eluted from the SKi Pro 
      system were collected and subjected to selected reaction monitoring LC-MS 
      characterization. Specific results were obtained for acetazolamide, DNSA, 
      furosemide and sulpiride. The results suggest that the association-dissociation 
      curve of a mixed sample can be obtained by one-time MIK-MS analysis. CONCLUSIONS: 
      Six small-molecule binders of CAII were analyzed quantitatively using nPOI and 
      MIK-MS, and the results were compared to published surface plasmon resonance 
      (SPR) results. The nPOI and SPR results show good agreement, confirming the 
      reliability of the analysis. Time-dependent binding results may be obtained by 
      our MS sensorgram approach. Drugs that meet medical needs in a short period are 
      required; this nPOI-LC-MS system is considered an important tool for rapid drug 
      discovery.
CI  - Copyright (c) 2018 John Wiley & Sons, Ltd.
FAU - Obi, Naoko
AU  - Obi N
AD  - Nissha Co. Ltd, Kyoto, Japan.
FAU - Fukuda, Tetsuya
AU  - Fukuda T
AD  - Biosys Technologies Inc., Tokyo, Japan.
FAU - Nakayama, Noboru
AU  - Nakayama N
AD  - Biosys Technologies Inc., Tokyo, Japan.
AD  - Translational Medicine Informatics, St Marianna University School of Medicine, 
      Research & Development, Biosys Technologies Inc., Tokyo, Japan.
FAU - Ervin, John
AU  - Ervin J
AD  - Silicon Kinetics Inc., San Diego, CA, USA.
FAU - Bando, Yasuhiko
AU  - Bando Y
AD  - Biosys Technologies Inc., Tokyo, Japan.
FAU - Nishimura, Toshihide
AU  - Nishimura T
AD  - Biosys Technologies Inc., Tokyo, Japan.
AD  - Translational Medicine Informatics, St Marianna University School of Medicine, 
      Research & Development, Biosys Technologies Inc., Tokyo, Japan.
FAU - Nagatoishi, Satoru
AU  - Nagatoishi S
AD  - Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
FAU - Tsumoto, Kouhei
AU  - Tsumoto K
AD  - School of Engineering, The University of Tokyo, Tokyo, Japan.
FAU - Kawamura, Takeshi
AU  - Kawamura T
AUID- ORCID: 0000-0003-1613-6968
AD  - Proteomics Laboratory, Isotope Science Center, The University of Tokyo, Tokyo, 
      Japan.
AD  - Laboratories for Systems Biology and Medicine (LSBM), Research Center for 
      Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Rapid Commun Mass Spectrom
JT  - Rapid communications in mass spectrometry : RCM
JID - 8802365
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Enzymes, Immobilized)
RN  - 0 (Ligands)
RN  - 0 (Small Molecule Libraries)
RN  - 7LXU5N7ZO5 (Furosemide)
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
RN  - Z4152N8IUI (Silicon)
SB  - IM
MH  - Carbonic Anhydrase II/*antagonists & inhibitors/*metabolism
MH  - Carbonic Anhydrase Inhibitors/chemistry/*pharmacology
MH  - Drug Evaluation, Preclinical/*instrumentation
MH  - Enzymes, Immobilized/metabolism
MH  - Equipment Design
MH  - Furosemide/chemistry/pharmacology
MH  - Humans
MH  - Interferometry/instrumentation
MH  - Kinetics
MH  - *Lab-On-A-Chip Devices
MH  - Ligands
MH  - Mass Spectrometry/*instrumentation
MH  - Porosity
MH  - Protein Binding
MH  - Silicon/chemistry
MH  - Small Molecule Libraries/chemistry/*pharmacology
EDAT- 2018/02/15 06:00
MHDA- 2018/09/05 06:00
CRDT- 2018/02/15 06:00
PHST- 2017/08/17 00:00 [received]
PHST- 2018/02/01 00:00 [revised]
PHST- 2018/02/02 00:00 [accepted]
PHST- 2018/02/15 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2018/02/15 06:00 [entrez]
AID - 10.1002/rcm.8083 [doi]
PST - ppublish
SO  - Rapid Commun Mass Spectrom. 2018 Apr 30;32(8):665-671. doi: 10.1002/rcm.8083.