Peptide T
| Peptide T | |
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L-Alanyl-L-seryl-L-threonyl-L-threonyl-L-threonyl-L-asparaginyl-L-tyrosyl-L-threonine |
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| Identifiers | |
| CAS number | 106362-32-7  |
| PubChem | 73352 |
| ChemSpider | 66081 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C35H55N9O16 |
| Molar mass | 857.86 g mol−1 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) | |
| Infobox references | |
Peptide T is an HIV entry inhibitor discovered in 1986 by National Institutes of Health (NIH) researchers.[1] Peptide T, and its modified analog Dala1-peptide T-amide (DAPTA), a drug in clinical trials, is a short peptide derived from the HIV envelope protein gp120 which blocks binding[2] and infection[3] of viral strains which use the CCR5 receptor to infect cells.
Peptide T has several positive effects related to HIV disease and Neuro-AIDS.[4] A placebo-controlled, three site, 200+ patient NIH-funded clinical trial, which focused on neurocognitive improvements, was conducted between 1990 and 1995. The results showed that peptide T was not significantly different from placebo on the study primary end points. However, peptide T was associated with improved performance in the subgroup of patients with more severe cognitive impairment.[5]
A long-delayed analysis of antiviral effects from the 1996 NIH study showed peripheral viral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group.[6] An eleven person study for peptide T effects on cellular viral load showed reductions in the persistently infected monocyte reservoir to undetectable levels in most of the patients.[7] Elimination of viral reservoirs, such as the monocytes, is an important treatment goal.[8] DAPTA has been shown to substantially suppress brain inflammation and block proinflammatory cytokine signaling pathways in a small animal model of Alzheimer's disease.[9]
[edit] References
- ^ Pert CB, Hill JM, Ruff MR et al. (Dec 1986). "Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity". Proc Natl Acad Sci USA. 83 (23): 9254–8. doi:10.1073/pnas.83.23.9254. PMC 387114. PMID 3097649. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3097649.
- ^ Polianova MT, Ruscetti FW, Pert CB, Ruff MR (Aug 2005). "Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA)". Antiviral Res. 67 (2): 83–92. doi:10.1016/j.antiviral.2005.03.007. PMID 16002156.
- ^ Ruff MR, Melendez-Guerrero LM, Yang QE et al. (Oct 2001). "Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5)". Antiviral Res. 52 (1): 63–75. doi:10.1016/S0166-3542(01)00163-2. PMID 11530189. http://linkinghub.elsevier.com/retrieve/pii/S0166-3542(01)00163-2.
- ^ Ruff MR, Polianova M, Yang QE, Leoung GS, Ruscetti FW, Pert CB (Jan 2003). "Update on D-ala-peptide T-amide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors". Curr HIV Res. 1 (1): 51–67. doi:10.2174/1570162033352066. PMID 15043212. http://www.bentham-direct.org/pages/content.php?CHR/2003/00000001/00000001/005AB.SGM.
- ^ Heseltine PN, Goodkin K, Atkinson JH et al. (Jan 1998). "Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment". Arch Neurol. 55 (1): 41–51. doi:10.1001/archneur.55.1.41. PMID 9443710. http://archneur.ama-assn.org/cgi/pmidlookup?view=long&pmid=9443710.
- ^ Goodkin K, Vitiello B, Lyman WD et al. (Jun 2006). "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment". J Neurovirol. 12 (3): 178–89. doi:10.1080/13550280600827344. PMID 16877299.
- ^ Polianova MT, Ruscetti FW, Pert CB et al. (Jul 2003). "Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA)". Peptides 24 (7): 1093–8. doi:10.1016/S0196-9781(03)00176-1. PMID 14499289. http://linkinghub.elsevier.com/retrieve/pii/S0196978103001761.
- ^ Crowe SM, Sonza S (Sep 2000). "HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: a further obstacle to eradication". J Leukoc Biol. 68 (3): 345–50. PMID 10985250. http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=10985250.
- ^ Rosi, S; Pert, C; Ruff, M; McGanngramling, K; Wenk, G (2005). "Chemokine receptor 5 antagonist -Ala-peptide T-amide reduces microglia and astrocyte activation within the hippocampus in a neuroinflammatory rat model of Alzheimer's disease". Neuroscience 134 (2): 671–6. doi:10.1016/j.neuroscience.2005.04.029. PMID 15979806.
