peptide-t-amide and HIV-Infections

peptide-t-amide has been researched along with HIV-Infections* in 2 studies

Reviews

1 review(s) available for peptide-t-amide and HIV-Infections

ArticleYear
Update on D-ala-peptide T-amide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors.
    Current HIV research, 2003, Volume: 1, Issue:1

    Peptide T, named for its high threonine content (ASTTTNYT), was derived by a database search which assumed that a relevant receptor binding epitope within env (gp120) would have sequence homology to a known signaling peptide. Binding of radiolabeled gp120 to brain membranes was displaced by peptide T and three octapeptide analogs (including "DAPTA", Dala1-peptide T-amide, the protease-resistant analog now in Phase II clinical trials) with the same potency that these four octapeptides blocked infectivity of an early passage patient isolate. This 1986 report was controversial due to a number of laboratories' failure to find peptide T antiviral effects; we now know that peptide T is a potent HIV entry inhibitor selectively targeting CCR5 receptors with minimal effects on the X4 tropic lab adapted virus exclusively in use at that time. Early clinical trials, which demonstrated lack of toxicity and focused on neurological and neurocognitive benefits, are reviewed and data from a small ongoing Phase II trial--the first to assess peptide T's antiviral effects--are presented. Studies using infectivity, receptor binding, chemotaxis, and blockade of gp120-induced neurotoxicity in vitro and in vivo are reviewed, discussed and presented here. Peptide T and analogs of its core pentapeptide, present near the V2 stem of numerous gp120 isolates, are potent ligands for CCR5. Clinical data showing peptide T's immunomodulation of plasma cytokine levels and increases in the percentage of IFNgamma secreting CD8+ T cells in patients with HIV disease are presented and suggests additional therapeutic mechanisms via regulation of specific immunity.

    Topics: CCR5 Receptor Antagonists; Clinical Trials, Phase II as Topic; HIV Infections; HIV-1; Humans; Peptide T; Receptors, HIV; Virus Replication

2003

Other Studies

1 other study(ies) available for peptide-t-amide and HIV-Infections

ArticleYear
Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA).
    Antiviral research, 2005, Volume: 67, Issue:2

    The chemokine receptor CCR5 plays a crucial role in transmission of HIV isolates, which predominate in the early and middle stages of infection, as well as those, which populate the brain and cause neuro-AIDS. CCR5 is therefore an attractive therapeutic target for design of entry inhibitors. Specific rapid filtration binding assays have been useful for almost 30 years both for drug discovery and understanding molecular mechanisms of drug action. Reported in 1986, prior to discovery of chemokine co-receptors and so thought to act at CD4, peptide T (DAPTA) appears to greatly reduce cellular viral reservoirs in both HAART experienced and treatment naïve patients, without toxicities. We here report that DAPTA potently inhibits specific CD4-dependent binding of gp120 Bal (IC50=0.06 nM) and CM235 (IC50=0.32 nM) to CCR5. In co-immunoprecipitation studies, DAPTA (1 nM) blocks formation of the gp120/sCD4 complex with CCR5. Confocal microscopic studies of direct FITC-DAPTA binding to CCR5+, but not CCR5-, cells show that CCR5 is a DAPTA receptor. The capability of DAPTA to potently block gp120-CD4 binding to the major co-receptor CCR5 explains its molecular and therapeutic mechanism of action as a selective antiviral entry inhibitor for R5 tropic HIV-1 isolates.

    Topics: CCR5 Receptor Antagonists; Cell Line; HIV Infections; HIV-1; Humans; Peptide T; Receptors, CCR5; Virus Replication

2005