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Preliminary studies on carbaborane-modified NPY derivatives show only minor changes in receptor binding and signal transduction. Therefore these compounds are very promising for future in vivo studies.

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SUMMARY We have developed a suitable synthesis employing the phosphoramidite method to connect meta-carbaboranyl bis-phosphonites with the 6´-OH group of iso- 10 propylidene-protected galactose, followed by oxidation or sulfurization to give the corresponding bis-phosphonates.

Deprotection yielded water-soluble compounds.

The corresponding disodium salts exhibit especially low cytotoxicity. The fully galactosylsubstituted derivatives are, however, less water soluble and show higher cytotoxicity.

Therefore, phosphinato-bridged bis meta-carbaborane derivatives seem to be more suitable also with respect to increasing the boron contents. In general, the bisphosphono-thioate derivatives exhibit higher cytotoxicity than the bis-phosphonato derivatives.

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Preliminary results on the in vivo toxicity and biodistribution of two compounds in mice indicated a lack of selectivity for the CRL tumor chosen for the experiment. Future studies will focus on different glycosides and their linkage with the phosphorus atom. Thus, glucose, mannose, or disaccharides such as lactose, amino sugars such as galactosamine, and different connectivities, e.

For the incorporation of carbaboranes into breast tumor selective neuropeptides, a synthesis of carbaborane-modified lysine derivatives was developed. Linkage of the lysine to the boron cluster was achieved by using a propanoic acid spacer.

Johnstown dating more convenient synthesis includes the linkage of the lysine to the thiol group at the B9 position of the carbaborane unit.

Incorporation of the amino acid derivatives into NPY by johnstown dating synthesis was successful. Preliminary studies show no significant changes in receptor binding affinity and signal transduction.

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We are grateful to Prof. Detlef Gabel, Universität Bremen, for enabling us to carry out the boron distribution studies in his group.

We thank Dr. Peter Lönnecke for X-ray structure determinations. Nakagawa, T. Kobayashi, H. Fukuda, Anticancer Res. WO A2. Cancer Res. Eur J Biochem.