"Click and go": simple and fast folic acid conjugation

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Trindade, AF (Author) Other; Frade, RFM (Author) Other; Macoas, EMS (Author) Other; Graca, C (Author) Other; Rodrigues, CAB (Author) Other; Martinho, JMG (Author) Other; Afonso, CAM (Author) Other

Journal

Title: Organic and Biomolecular Chemistry

Vol. 12

Pages: 3181-3190

ISSN: 1477-0520

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 32 Citations

Other information

Authenticus ID: P-009-9VG

DOI: 10.1039/c4ob00150h

Abstract (EN): Folic acid targeting by functionalization of the terminal gamma-carboxylic acid is one of the most important strategies to selectively deliver chemotherapeutics and dyes to cancer cells which overexpress folate receptors. However, conjugation of folic acid is limited by its unique solubility and by selectivity issues imposing the need for expensive preparative reverse-phase chromatographic purification to isolate gamma-folate conjugates. Herein is provided a novel synthetic tool for the synthesis of new folic acid conjugates with excellent gamma-purity based on strain-promoted alkyne-azide cycloadditions with a gamma-folate-cyclooctyne conjugate 3. To demonstrate the potential of this methodology several new folate conjugates were synthesized with high gamma-purity and without using any type of chromatographic purification by reacting conjugate 3 with several fluorescent probes, polymers and siliceous materials bearing azide. In addition, the cycloaddition reaction between conjugate 3 and an azido-derived fluorescent dye was successfully performed in cellular media leading to an increase of fluorescence in the cells which overexpress folate receptors (NCI-H460).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10