Tuftsin-AZT conjugate: potential macrophage targeting for AIDS therapy.
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.
Fridkin
Mati
M
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel 76100. mati.fridkin@weizmann.ac.il
Tsubery
Haim
H
Tzehoval
Esther
E
Vonsover
Ami
A
Biondi
Laura
L
Filira
Fernando
F
Rocchi
Raniero
R
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D017951:Antigen Presentation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers; D015195:Drug Design; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D019380:Anti-HIV Agents; D004337:Drug Carriers; D007375:Interleukin-1; D018894:Reverse Transcriptase Inhibitors; C501870:tuftsin-AZT conjugate; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D014405:Tuftsin