Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Rusnati, Marco; Urbinati, Chiara; Caputo, Antonella; Possati, L; Lortat‐Jacob, Hugues; Giacca, Mauro; Ribatti, Doménico; Presta, Marco

doi:10.1074/jbc.m010779200

Cited by 69 publications

(64 citation statements)

References 39 publications

(74 reference statements)

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“…These data indicate that, at variance with heparin, PTX-B did not sequester Tat in the extracellular environment. Accordingly, binding experiments performed by BIAcore technology [28] confirmed that PTX-B does not bind Tat (data not shown).…”

Section: Ptx-b Inhibits Intracellular and Extracellular Hiv-1 Tat-medmentioning

confidence: 83%

“…Heparin and other extracellular Tat antagonists inhibit Tat function by binding and sequestering it in the extracellular environment, thus hampering its interaction with target cells [28]. We then investigated if PTX-B prevents Culture medium containing PTX-B was completely removed at the indicated times, and GST-Tat was then added.…”

Section: Ptx-b Inhibits Intracellular and Extracellular Hiv-1 Tat-medmentioning

confidence: 99%

“…HL3T1 cells were transfected with the pCEP-Tat expression vector by lipofectin (Invitrogen, Carlsbad, CA) as previously described [28]. Alternatively, HL3T1 cells were incubated with GST-Tat in the presence of chloroquine [27].…”

Section: Hiv-1 Ltr Transactivation Assaymentioning

confidence: 99%

“…Observations were carried out with a photomicroscope equipped for epifluorescence (Zeiss, Göttingen, Germany) and GST-Tat-GFPinternalization was quantified by computerized image analysis as described [28]. The values of Tat-integrated optical density obtained for GST-Tat-GFP-treated and untreated cells were equal to 235±76 and 6±7, respectively.…”

Section: Internalization Of Gst-tat-gfp In Hl3t1 Cellsmentioning

confidence: 99%

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Inhibition of intra‐ and extra‐cellular Tat function and HIV expression by pertussis toxin B‐oligomer

et al. 2004

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HIV‐1‐transactivating factor Tat contributes to virus replication and to the onset of AIDS‐associated pathologies by targeting different infected and uninfected cell types. We previously demonstrated that the B‐oligomer of pertussis toxin (PTX‐B) inhibits HIV infection and replication in primary T cells and macrophages and Tat‐dependent HIV‐1 long terminal repeat (LTR) transactivation inT lymphoid Jurkat cells. Here we demonstrate that PTX‐B inhibits Tat‐dependent NF‐κB activation and HIV‐1 LTR‐transactivation in non‐permissive epithelial HL3T1 cells in a phosphatidylinositol 3′‐kinase‐dependent way. PTX‐B exerts its inhibition both when Tat is produced endogenously in transfected cells and in cells incubated with the extracellular Tat protein. In this latter case, PTX‐B does not interfere with extracellular Tat uptake by cells. PTX‐B inhibited also interleukin‐8 secretion and virus expression stimulated in chronically infected U1 promonocytic cells by intra‐ and/or extracellular Tat. The genetically modified holotoxin PT‐9 K/129G retains the capacity to inhibit Tat transactivating activity and HIV replication in both HIV‐permissive and non‐permissive cells. Inconclusion, PTX‐B acts as a "pleiotropic" inhibitor of Tat, and this may significantly contribute to the broad spectrum of anti‐HIV‐1 effects exerted by PTX‐B in different cell types, and suggests PTX‐B and its derivatives as prototypic for the development of anti‐Tat drugs.

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Section: Ptx-b Inhibits Intracellular and Extracellular Hiv-1 Tat-medmentioning

confidence: 83%

Section: Ptx-b Inhibits Intracellular and Extracellular Hiv-1 Tat-medmentioning

confidence: 99%

Section: Hiv-1 Ltr Transactivation Assaymentioning

confidence: 99%

Section: Internalization Of Gst-tat-gfp In Hl3t1 Cellsmentioning

confidence: 99%

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Inhibition of intra‐ and extra‐cellular Tat function and HIV expression by pertussis toxin B‐oligomer

et al. 2004

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“…In several studies, initial ionic interactions at the cell membrane 7 surface have been however shown to be key determinants for the uptake of all the cationic CPPs since the peptide entry could be strongly reduced by competition with polyanionic compounds [51][52][53][54] or by stringent cell washes with solutions at acidic pH [55].…”

Section: Cpps and Cell Entrymentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

317

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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Fabrication of Carbohydrate Surfaces by Using Nonderivatised Oligosaccharides, and their Application to Measuring the Assembly of Sugar–Protein Complexes

Popplewell¹,

Swann²,

Ahmed

et al. 2009

ChemBioChem

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This way up. Dual polarisation interferometry was used to design and characterise a surface on which the orientation and density of immobilised carbohydrates was suitable for studying their interactions with proteins. Lactoferrin was shown to adopt two orientations: "end-on" or "side-on", while for FGF-2 a single monolayer of protein was observed. The new surface can be used to elucidate the binding of proteins to carbohydrates and the geometry of the complexes, a frequently controversial area. Surface-based tools, such as microarrays and optical biosensors, are being increasingly applied to the analysis of carbohydrate-protein interactions. A key to these developments is the presentation of the carbohydrate to the protein target. Dual polarisation interferometry (DPI) is a surface-based technique that permits the real-time measurement of the changes in thickness, refractive index and mass of adsorbates 100 nm thick or less on the surface of a functionalised waveguide. DPI has been used to design and characterise a surface on which the orientation and density of the immobilised carbohydrates is suitable for studying their interactions with proteins and where nonspecific binding is reduced to less than 5 % of total binding. A thiol-functionalised surface was derivatised with a heterobifunctional crosslinker to yield a hydrazide surface. This was treated with oligosaccharides, derived from keratan sulfate (KS) chondroitin sulfate (CS) and heparin, that possess a reducing end. To block the unreacted hydrazide groups, the surface was treated with an aldehyde-functionalised PEG. The heparin DP-10 surfaces were then used to determine the performance of the immobilised DP-10 with respect to binding of two well-characterised proteins, lactoferrin (Lf) and fibroblast growth factor-2. The results show that Lf could adopt two different orientations, at high protein loadings the protein layer thickness corresponded to an "end-on" orientation of Lf, whilst rinsing with buffer saw the Lf molecules adopt a "side-on" configuration. In the case of FGF-2, a single monolayer of protein bound to DP-10 was observed. These results demonstrate that the new surface can be used to resolve key questions relating to the binding of proteins to carbohydrates, including, when used in DPI, the resolution of the geometry of complexes, an area that is frequently controversial.

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Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat

Cited by 69 publications

References 39 publications

Inhibition of intra‐ and extra‐cellular Tat function and HIV expression by pertussis toxin B‐oligomer

Inhibition of intra‐ and extra‐cellular Tat function and HIV expression by pertussis toxin B‐oligomer

Cell-penetrating and cell-targeting peptides in drug delivery

Fabrication of Carbohydrate Surfaces by Using Nonderivatised Oligosaccharides, and their Application to Measuring the Assembly of Sugar–Protein Complexes

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