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Tuftsin-AZT conjugate: potential macrophage targeting for AIDS therapy.

Fridkin M, Tsubery H, Tzehoval E, Vonsover A, Biondi L, Filira F, Rocchi R

Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel 76100. mati.fridkin@weizmann.ac.il

The IgG-derived immunomodulating peptide tuftsin, Thr-Lys-Pro-Arg, is recognized by specific receptors on phagocytic cells, notably macrophages, and is capable of targeting proteins and peptides to these sites. Aiming to target 3'-azido-3'-deoxythymidine (AZT) to HIV-infected macrophages, a conjugate of AZT with tuftsin was synthesized. The AZT-tuftsin chimera possesses the characteristic capacities of its two components. Thus, like AZT, it inhibits reverse transcriptase activity and HIV-antigen expression, and similarly to tuftsin, it stimulates IL-1 release from mouse macrophages and augments the immunogenic function of the cells. Importantly, the conjugate is not cytotoxic to T-cells. The results suggest that the AZT-tuftsin conjugate might have potential use in AIDS therapy.

Published 6 January 2005 in J Pept Sci, 11(1): 37-44.
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