Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720

FTY720 ( 1) is a novel immunosuppressant (immunomodulator), derived from ISP-I ( 2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were sy...

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Published in:Bioorganic & medicinal chemistry 2006-06, Vol.14 (12), p.4182-4192
Main Authors: Matsumoto, Norimasa, Kohno, Takeyuki, Uchida, Shuji, Shimizu, Takaaki, Kusumoto, Haruko, Hirose, Ryoji, Yanada, Kazuo, Kurio, Wasako, Yamaguchi, Shoji, Watabe, Kazuhito, Fujita, Tetsuro
Format: Article
Language:English
Subjects:
Administration, Oral
Analysis
Animals
Antibodies - chemistry
Antibodies - pharmacology
Antigen-Antibody Reactions
Biological and medical sciences
Enzyme immunoassay
Female
Fingolimod Hydrochloride
FTY720
General pharmacology
Hapten
Haptens - chemistry
Immunoenzyme Techniques - methods
Immunosuppressant
Medical sciences
Molecular Structure
Ovalbumin - chemistry
Pharmacology. Drug treatments
Propylene Glycols - administration & dosage
Propylene Glycols - antagonists & inhibitors
Propylene Glycols - chemistry
Rabbits
Sphingosine - administration & dosage
Sphingosine - analogs & derivatives
Sphingosine - antagonists & inhibitors
Sphingosine - chemistry
Stereoisomerism
Structure-Activity Relationship
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Summary:FTY720 ( 1) is a novel immunosuppressant (immunomodulator), derived from ISP-I ( 2: myriocin and thermozymocidin). To clarify the pharmacokinetic properties of 1, antibodies against 1 were prepared and a competitive enzyme immunoassay (EIA) was developed. Two kinds of haptens, 3 and 4, for 1 were synthesized and coupled to ovalbumin (OVA). Rabbits were immunized with 3-OVA or 4-OVA, and corresponding antibodies were obtained. Both antibodies recognized the 2-amino-2-(2-phenylethyl)propane-1,3-diol moiety in 1. Using the anti- 3-OVA antibody, a competitive EIA for 1 was developed and evaluated. The range of quantification by the EIA was 0.06–10 ng/mL. The application of the EIA has enabled us to measure the FTY720 concentration in serum after oral administration of 1 (1 mg/kg) to rats.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2006.01.071