Carbohydration of branches ligands with a cyclam-core

Radiopharmaceuticals based on the metallic radionuclides ^64/67Cu, ^99mTc, ^186/188Re and ⁹⁰Y are often used for diagnostic and therapeutic purposes. Cyclam and its derivatives are one of the most important ligands for the radionuclides mentioned above.[1] A ^99mTc-labelled cyclam derivative with attached nitro-triazole units has the potential to be utilized as a marker for tumor hypoxia.[2] Promising tumor accumulation properties have been found for a ^99mTc complex of a water-soluble cyclam-containing porphyrin.[3] Recently, we could show that a star-like cyclam ligand appended with four PEG-arms rapidly forms stable copper(II) complexes.[4] Currently, we are focusing our attention on the development of dendritic ligands having both enhanced complex stability and improved bio-availability. In this nexus, we built up two glycodendrimers possessing a cyclam core modified with thiourea-linked sugar residues at the periphery of the molecule (see scheme). Dendrons possessing such sugar moieties show both unique cell uptake behaviour and specific carbohydrate-protein interaction.[5, 6]

We want to report the ^99mTc-labelling of the dendritic ligands synthesized. Furthermore, the interaction of these ligands with concanavalin A has been studied using isothermal titration microcalorimetry. In this nexus, a cluster glycoside effect could be clearly shown.[7]

REFERENCES
[1] X. Liang, P. Sadler, Chem. Soc. Rev. 2004, 33, 246-266.
[2] S. Murugesan, S. J. Shetty, O. P. D. Noronha, A. M. Samuel, T. S. Srivastava, C. K. K. Nair, L. Kothari, Appl. Radiat. Isot. 2001, 54, 81-88.
[3] S. Murugesan, S. J. Shetty, T. S. Srivastava, O. P. D. Noronha, A. M. Samuel, Appl. Radiat. Isot. 2001, 55, 641-646.
[4] H. Stephan, G. Geipel, D. Appelhans, G. Bernhard, D. Tabuani, H. Komber, B. Voit, Tetrahedron Lett. 2005, 46, 3209-3212.
[5] L. Vannucci, A. Fiserova, K. Sadalapure, T. K. Lindhorst, M. Kuldova,, P. Rossmann, O. Horvath, V. Kren, P. Krist, K. Bezouska, M. Luptovcova, F. Mosca, M. Pospisil, Int. J. Oncology 2003, 23, 285-296.
[6] P. Krist, L. Vannucci, M. Kuzma, P. Man, K. Sadalapure, A. Patel, K. Bezouska, M. Pospisil, L. Petrus, T. K. Lindhorst, V. Kren, CHEMBIOCHEM 2004, 5, 445-452.