Design and regioselective synthesis of a new generation of targeted therapeutics. Part 3: Folate conjugates of aminopterin hydrazide for the treatment of inflammation |
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Authors: | Vlahov Iontcho R You Fei Santhapuram Hari Krishna R Wang Yu Vaughn Jeremy F Hahn Spencer J Kleindl Paul J Fan Mingjin Leamon Christopher P |
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Affiliation: | Endocyte Inc., 3000 Kent Ave, Suite A1-100, West Lafayette, IN 47906, USA |
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Abstract: | Efficient syntheses of folate receptor (FR) targeting conjugates of the anti-inflammatory, aminopterin hydrazide, are described. 2-{4-Benzoylamino}-5-oxo-5-{N′-[2-(pyridin-2-yldisulfanyl)-ethoxycarbonyl]-hydrazino}-pentanoic acid is synthesized from commercially available 4-[(2-amino-4-imino-3,4-dihydro-pteridin-6-yl-methyl)-amino]-benzoic acid. Conjugation of this novel, activated aminopterin hydrazide to folic acid through cysteine-terminating (C-terminus), peptide/carbohydrate spacers results in highly water soluble conjugates which allow for the release of free aminopterin hydrazide within the endosomes of targeted cells. |
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Keywords: | Folate Folate receptor targeting Folate-aminopterin hydrazide conjugate Inflammation Disulfide linkers |
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