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Current HIV Research
ISSN (Print): 1570-162X
ISSN (Online): 1873-4251
VOLUME: 1
ISSUE: 1
DOI: 10.2174/1570162033352066









Update on D-Ala-Peptide T-Amide (DAPTA): A Viral Entry Inhibitor that Blocks CCR5 Chemokine Receptors

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Author(s): Michael R. Ruff, Maria Polianova, Quan-en Yang, Gifford S. Leoung, Francis W. Ruscetti and Candace B. Pert
Pages 51-67 (17)
Abstract:
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 Ts 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 Ts immunomodulation of plasma cytokine levels and increases in the percentage of IFN? secreting CD8+ T cells in patients with HIV disease are presented and suggests additional therapeutic mechanisms via regulation of specific immunity.
Keywords:
peptide t, entry inhibitor, immune reconstitution, antiviral, ifn, chemokine, cytokine, reservoir
Affiliation:
Department of Physiology and Biophysics, School of Medicine, Georgetown University, Box 571460, Washington, D.C. 20057-1460