Methods and Compositions for Inhibiting HIV-Coreceptor Interactions
Description of Invention:
This invention provides peptides that might be potent inhibitors of HIV replication, in both macrophages and T lymphocytes. Specifically, the inventors have identified peptides, from the HIV-1 gp120 envelope protein, that share structural similarities with chemokines and are shown to block "docking" interactions between the HIV-1 envelope protein gp120 and chemokine receptors that function as "coreceptors" for HIV entry on the surface of target cells (macrophages and T lymphocytes). The inventors synthesized two peptides (designated 15K and 15D) based on this information and showed that both were effective in competing with chemokines for binding to CCR5- and CXCR4-expressing cells. These peptides efficiently inhibited infection of human monocyte derived macrophages and peripheral blood mononuclear cells by different strains of HIV. The synthesized peptides also inhibited monocyte chemotaxis stimulated by the chemokine RANTES. Thus, these peptides and other molecules based on their structure can be potentially used as inhibitors of HIV. Moreover, these peptides could also have anti-inflammatory and anti-tumor activity. Further, it has been determined that these peptides are multi-tropic in their effects (blocking HIV interactions with multiple co-receptors) for blocking both T cell tropic (lymphotropic) and macrophage tropic (m-tropic) HIV strains.
Inventors:
Oleg Chertov (NCI) Joost J. Oppenheim (NCI) Xin Chen (NCI) Connor McGrath (NCI) Raymond C. Sowder II (NCI) Jacek Lubkowski (NCI) Michele Wetzel (EM) Thomas J. Rogers (EM)
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics Infectious Diseases -Therapeutics
For Additional Information Please Contact: Sally Hu PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5606
Email: hus@mail.nih.gov
Fax: (301) 402-0220
