Novel synthesis of fluorochrome-coupled zoledronate with preserved functional activity on gamma/delta T cells and tumor cells

Vijayanand Chandrasekaran; Shirin Kalyan; Valentina Biel; Marcus Lettau; Patrik Theodor Nerdal; Hans-Heinrich Oberg; Daniela Wesch; Thisbe K. Lindhorst; Dieter Kabelitz

doi:10.1039/C5MD00063G

Novel synthesis of fluorochrome-coupled zoledronate with preserved functional activity on gamma/delta T cells and tumor cells

Vijayanand Chandrasekaran,^a Shirin Kalyan,^b Valentina Biel,^b Marcus Lettau,^b Patrik Theodor Nerdal,^b Hans-Heinrich Oberg,^b Daniela Wesch,^b Thisbe K. Lindhorst^a and Dieter Kabelitz*^b

Author affiliations

* Corresponding authors

^a Otto Diels Institute of Organic Chemistry, Christian-Albrechts-University of Kiel, Otto-Hahn-Platz 3, D-24118 Kiel, Germany

^b Institute of Immunology, Christian-Albrechts-University of Kiel, Arnold-Heller-Straße 3, Bldg. 17, D-24105 Kiel, Germany
E-mail: dietrich.kabelitz@uksh.de
Fax: +49 431 5973335
Tel: +49 431 5793340

Abstract

In addition to their effects on bone resorption, nitrogen-containing bisphosphonates (N-BP) selectively activate γδ T cells, an innate-like immune cell population with potent anti-tumor activity. N-BP stimulate γδ T cells through induction of intracellular accumulation of mevalonate pathway-derived pyrophosphates, which are strong and selective antigens for human γδ T cells. The most potent among several classes of N-BP is zoledronate (ZOL). To study the uptake of ZOL and its immunological consequences in the γδ T cell/tumor cell interplay, we have synthesized a novel fluorescently labeled ZOL derivative termed FluorZOL by covalently coupling ZOL to carboxyfluorescein succinidimyl ester. Here we describe in detail the synthesis of FluorZOL and we further show that FluorZOL is functionally fully active as revealed by the selective expansion of γδ T cells and the enhancement of tumor cell lysis by γδ T cells.

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Publication details

The article was received on 13 Feb 2015, accepted on 26 Mar 2015 and first published on 30 Mar 2015

Article type: Concise Article

DOI: 10.1039/C5MD00063G

Citation: Med. Chem. Commun., 2015,6, 919-925

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Novel synthesis of fluorochrome-coupled zoledronate with preserved functional activity on gamma/delta T cells and tumor cells

V. Chandrasekaran, S. Kalyan, V. Biel, M. Lettau, P. T. Nerdal, H. Oberg, D. Wesch, T. K. Lindhorst and D. Kabelitz, Med. Chem. Commun., 2015, 6, 919
DOI: 10.1039/C5MD00063G
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Novel synthesis of fluorochrome-coupled zoledronate with preserved functional activity on gamma/delta T cells and tumor cells

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Novel synthesis of fluorochrome-coupled zoledronate with preserved functional activity on gamma/delta T cells and tumor cells

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