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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.<ref>{{cite journal |author=Goodkin K |title=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 |journal=J Neurovirol. |volume=12 |issue=3 |pages=178–89 |date=Jun 2006 |pmid=16877299 |doi=10.1080/13550280600827344 |name-list-format=vanc|author2=Vitiello B |author3=Lyman WD |display-authors=3 |last4=Asthana |first4=Deshratn |last5=Atkinson |first5=J Hampton |last6=Heseltine |first6=Peter NR |last7=Molina |first7=Rebeca |last8=Zheng |first8=Wenli |last9=Khamis |first9=Imad }}</ref> 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.<ref>{{cite journal |author=Polianova MT |title=Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA) |journal=Peptides |volume=24 |issue=7 |pages=1093–8 |date=Jul 2003 |pmid=14499289 |url=http://linkinghub.elsevier.com/retrieve/pii/S0196978103001761 |doi=10.1016/S0196-9781(03)00176-1 |name-list-format=vanc|author2=Ruscetti FW |author3=Pert CB |display-authors=3 |last4=Tractenberg |first4=RE |last5=Leoung |first5=G |last6=Strang |first6=S |last7=Ruff |first7=MR}}</ref> Elimination of viral reservoirs, such as the monocytes, is an important treatment goal.<ref>{{cite journal |author=Crowe SM, Sonza S |title=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 |journal=J Leukoc Biol. |volume=68 |issue=3 |pages=345–50 |date=Sep 2000 |pmid=10985250 |url=http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=10985250}}</ref> DAPTA has been shown to substantially suppress brain inflammation and block proinflammatory cytokine signaling pathways in a small animal model of [[Alzheimer's disease]].<ref>{{cite journal|doi=10.1016/j.neuroscience.2005.04.029|title=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|year=2005|last1=Rosi|first1=S|last2=Pert|first2=C|last3=Ruff|first3=M|last4=McGanngramling|first4=K|last5=Wenk|first5=G|journal=Neuroscience|volume=134|issue=2|pages=671–6|pmid=15979806 }}</ref>
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.<ref>{{cite journal |author=Goodkin K |title=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 |journal=J Neurovirol. |volume=12 |issue=3 |pages=178–89 |date=Jun 2006 |pmid=16877299 |doi=10.1080/13550280600827344 |name-list-format=vanc|author2=Vitiello B |author3=Lyman WD |display-authors=3 |last4=Asthana |first4=Deshratn |last5=Atkinson |first5=J Hampton |last6=Heseltine |first6=Peter NR |last7=Molina |first7=Rebeca |last8=Zheng |first8=Wenli |last9=Khamis |first9=Imad }}</ref> 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.<ref>{{cite journal |author=Polianova MT |title=Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA) |journal=Peptides |volume=24 |issue=7 |pages=1093–8 |date=Jul 2003 |pmid=14499289 |url=http://linkinghub.elsevier.com/retrieve/pii/S0196978103001761 |doi=10.1016/S0196-9781(03)00176-1 |name-list-format=vanc|author2=Ruscetti FW |author3=Pert CB |display-authors=3 |last4=Tractenberg |first4=RE |last5=Leoung |first5=G |last6=Strang |first6=S |last7=Ruff |first7=MR}}</ref> Elimination of viral reservoirs, such as the monocytes, is an important treatment goal.<ref>{{cite journal |author=Crowe SM, Sonza S |title=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 |journal=J Leukoc Biol. |volume=68 |issue=3 |pages=345–50 |date=Sep 2000 |pmid=10985250 |url=http://www.jleukbio.org/cgi/pmidlookup?view=long&pmid=10985250}}</ref> DAPTA has been shown to substantially suppress brain inflammation and block proinflammatory cytokine signaling pathways in a small animal model of [[Alzheimer's disease]].<ref>{{cite journal|doi=10.1016/j.neuroscience.2005.04.029|title=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|year=2005|last1=Rosi|first1=S|last2=Pert|first2=C|last3=Ruff|first3=M|last4=McGanngramling|first4=K|last5=Wenk|first5=G|journal=Neuroscience|volume=134|issue=2|pages=671–6|pmid=15979806 }}</ref>

Peptide T is NOT approved anywhere in the world.


==Popular culture==
==Popular culture==

Revision as of 02:22, 15 November 2015

Peptide T
Names
IUPAC name
L-Alanyl-L-seryl-L-threonyl-L-threonyl-L-threonyl-L-asparaginyl-L-tyrosyl-L-threonine
Identifiers
3D model (JSmol)
ChemSpider
  • InChI=1S/C35H55N9O16/c1-13(36)28(52)40-22(12-45)31(55)41-25(15(3)47)33(57)43-26(16(4)48)34(58)42-24(14(2)46)32(56)39-21(11-23(37)51)29(53)38-20(10-18-6-8-19(50)9-7-18)30(54)44-27(17(5)49)35(59)60/h6-9,13-17,20-22,24-27,45-50H,10-12,36H2,1-5H3,(H2,37,51)(H,38,53)(H,39,56)(H,40,52)(H,41,55)(H,42,58)(H,43,57)(H,44,54)(H,59,60)/t13-,14+,15+,16+,17+,20-,21-,22-,24-,25-,26-,27-/m0/s1
    Key: IWHCAJPPWOMXNW-LYKMMFCUSA-N
  • InChI=1/C35H55N9O16/c1-13(36)28(52)40-22(12-45)31(55)41-25(15(3)47)33(57)43-26(16(4)48)34(58)42-24(14(2)46)32(56)39-21(11-23(37)51)29(53)38-20(10-18-6-8-19(50)9-7-18)30(54)44-27(17(5)49)35(59)60/h6-9,13-17,20-22,24-27,45-50H,10-12,36H2,1-5H3,(H2,37,51)(H,38,53)(H,39,56)(H,40,52)(H,41,55)(H,42,58)(H,43,57)(H,44,54)(H,59,60)/t13-,14+,15+,16+,17+,20-,21-,22-,24-,25-,26-,27-/m0/s1
    Key: IWHCAJPPWOMXNW-LYKMMFCUBM
  • O=C(N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)[C@H](O)C)Cc1ccc(O)cc1)CC(=O)N)[C@H](O)C)[C@H](O)C)[C@H](O)C)CO)[C@@H](N)C
Properties
C35H55N9O16
Molar mass 857.872 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Peptide T is an HIV entry inhibitor discovered in 1986 by researchers at the National Institutes of Health in the United States.[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]

Peptide T is NOT approved anywhere in the world.

In the biographical film drama Dallas Buyers Club,[10] protagonist Ron Woodroof (Matthew McConaughey) promotes the use of injected peptide T as a treatment for HIV/AIDS and Alzheimer's Disease.

References

  1. ^ 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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  2. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ 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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  4. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ 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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  6. ^ 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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  7. ^ 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. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  8. ^ 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.
  9. ^ 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.
  10. ^ Dallas Buyers Club. Dir. Jean-Marc Vallée. Perf. Matthew McConaughey. Truth Entertainment, Voltage Pictures; Focus Features (US), 2013.
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