Introduction
DAPTA (D-[Ala]-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-amide), D-Ala-Peptide T amide, is one of analogue of peptide T, which is an octapeptides from the V2 region of gp120 of HIV, named for its high threonine content. It is a non-toxic experimental antiviral entry inhibitor and inhibits the binding of HIV envelope to brain membranes as well as the HIV infection of human T cells in vitro. This is the first viral entry inhibitor that blocks chemokine (CCR5) receptors, not CD4.
Biological Activity
DAPTA, derived from the V2 region, near the stem of HIV-1SF-2 env protein (amino acids 185-192), blocks infection of R5 and dual tropic (R5/X4) HIV-1 strains in monocyte-derived macrophages, microglia and primary CD4+ T-cells and is an antagonist of CCR5-mediated chemotaxis. A highly active antiretroviral therapy (HAART) placebo-controlled trial showed that DAPTA caused cognitive improvements, and a later analysis of stored samples suggests a clinically significant reduction in plasma viral load. A recent uncontrolled clinical trial reports that DAPTA substantially suppresses virus in persistently infected cellular reservoirs in both HAART experienced and naive to treatment patients.
Function
The ability of DAPTA to block CCR5 plays a crucial role in transmission of HIV isolates, which predominates in the early and middle stages of infection and populates the brain to cause neuro-AIDS. , as well as those, which Therefore, DAPTA is tested as therapeutic agent for the treatment of HIV infection, and it also has been shown to resolve the psoriatic lesions. This non-toxic small peptide suppresses the infection of peripheral blood monocytes, and thereby prevents and reduces the population of infected differentiated M/M (Monocytes/macrophages), which have an important role in all phases of human immunodeficiency virus type 1 (HIV-1) infection, acting as a vehicle for virus dissemination in the body and representing the major reservoir for long-term persistence of HIV-1 during HAART. In a small clinical trial, DAPTA has shown promising antiviral and immune benefits. Moreover, the peptide contributes to improvements in cognition in humans with HIV-1 infection, which also suggests its penetration into the central nervous system (CNS).
References:
1. Ruff, M. R., Polianova, M., Yang, Q. E., Leoung, G. S., Ruscetti, F. W., & Pert, C. B. (2003). Update on D-ala-peptide T-amide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors. Current HIV research, 1(1), 51-67.
2. Polianova, M. T., Ruscetti, F. W., Pert, C. B., Tractenberg, R. E., Leoung, G., Strang, S., & Ruff, M. R. (2003). Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA). Peptides, 24(7), 1093-1098.
3. Polianova, M. T., Ruscetti, F. W., Pert, C. B., & Ruff, M. R. (2005). Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA). Antiviral research, 67(2), 83-92.
4. Raychaudhuri, S. K., Raychaudhuri, S. P., & Farber, E. M. (1998). Anti-chemotactic activities of peptide-T: a possible mechanism of actions for its therapeutic effects on psoriasis. International journal of immunopharmacology, 20(11), 661-667.
5. Pollicita, M., Ruff, M. R., Pert, C. B., Polianova, M. T., Schols, D., Ranazzi, A., ... & Aquaro, S. (2007). Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells. Antiviral Chemistry and Chemotherapy, 18(5), 285-295.
