Synthesis of a fluorescent derivative of amethopterin

Fluorescein isothiocyanate was treated with excess diaminopentane and the remaining unsubstituted amino group of the product was condensed, via a carbodiimide-promoted reaction, with a carboxyl group of amethopterin. The final product, a fluorescent derivative of amethopterin, was isolated by chroma...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1975-05, Vol.18 (5), p.526-528
Main Authors: Gapski, G. R, Whiteley, J. M, Rader, J. I, Cramer, P. L, Hendersen, G. B, Neef, V, Huennekens, F. M
Format: Article
Language:English
Subjects:
Animals
Biological Transport - drug effects
Depression, Chemical
Diamines
Fluoresceins
Fluorescence
Folic Acid Antagonists
Lactobacillus casei - enzymology
Leukemia L1210 - enzymology
Methotrexate - analogs & derivatives
Methotrexate - chemical synthesis
Methotrexate - pharmacology
Spectrophotometry, Ultraviolet
Thiocyanates
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Summary:Fluorescein isothiocyanate was treated with excess diaminopentane and the remaining unsubstituted amino group of the product was condensed, via a carbodiimide-promoted reaction, with a carboxyl group of amethopterin. The final product, a fluorescent derivative of amethopterin, was isolated by chromatography on AE-cellulose and preparative electrophoresis on polyacrylamide. It was shown to be homogeneous by analytical polyacrylamide electrophoresis and thin-layer chromatography. Proof of structure was provided by elemental analysis, absorbance spectra (at pH 7.0, lambdamax at 495 nm; fluorescence emission at 520 nm), and 1H NMR measurements. The fluorescent derivative of amethopterin inhibited transport of amethopterin into Lactobacillus casei and L1210 cells. It was also a good inhibitor of the L. casei and L1210 dihydrofolate reductases and could be used to provide a fluorescent label for the enzymes during polyacrylamide electrophoresis.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00239a020