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

Abstract

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.

• Authors: Mati Fridkin, Haim Tsubery, Esther Tzehoval, Ami Vonsover, Laura Biondi, Fernando Filira, Raniero Rocchi
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 11 Issue 1 Pg. 37-44 (Jan 2005) ISSN: 1075-2617 [Print] England
• PMID: 15635725 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2004 European Peptide Society and John Wiley & Sons, Ltd.

Chemical References

• Anti-HIV Agents
• Drug Carriers
• Interleukin-1
• Reverse Transcriptase Inhibitors
• tuftsin-AZT conjugate
• Zidovudine
• HIV Reverse Transcriptase
• Tuftsin

Topics

• Animals
• Anti-HIV Agents (pharmacology, toxicity)
• Antigen Presentation
• Cell Line
• Cell Survival (drug effects)
• Cells, Cultured
• Drug Carriers
• Drug Design
• Female
• HIV Reverse Transcriptase (antagonists & inhibitors, metabolism)
• HIV-1 (drug effects, physiology)
• Humans
• Interleukin-1 (metabolism)
• Macrophages (drug effects, immunology, virology)
• Mice
• Reverse Transcriptase Inhibitors (pharmacology, toxicity)
• Tuftsin (analogs & derivatives, chemical synthesis, pharmacology, toxicity)
• Virus Replication (drug effects)
• Zidovudine (analogs & derivatives, chemical synthesis, pharmacology, toxicity)