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• W2275564897 endingPage "1425" @default.
• W2275564897 startingPage "1418" @default.
• W2275564897 abstract "Small compounds capable of blocking the stromal cell-derived factor 1 (SDF-1) receptor CXCR4 may be potentially useful as anti-inflammatory, antiallergic, immunomodulatory, and anti-human immunodeficiency virus (HIV) agents. SDF-1–derived peptides have proven to target CXCR4 efficiently despite a 100-fold lower affinity (or more) than SDF-1. Here we studied the binding and antiviral properties of a series of substituted SDF-1–derived N-terminal peptides and tested their functional effects on human polymorphonuclear cells, because these cells are very reactive to chemokines and chemoattractants. All peptides bound to CXCR4 and inhibited HIV entry in a functional assay on CD4⁺ HeLa cells. A 10-residue substituted dimer, derived from the 5–14 sequence of SDF-1, displayed the highest affinity for CXCR4 (<i>K</i>_i value of 290 nM, a reduction of only 15-fold compared with SDF-1) and was also the best competitor for HIV entry (IC₅₀ value of 130 nM). Whereas most peptides displayed CXCR4-independent functional effects on human polymorphonuclear cells, including the modulation of calcium fluxes and the activation of superoxide anion production at high concentration (10 μM), the peptide dimer was devoid of these nonspecific effects at antiviral concentrations. Overall, this study shows that appropriate modifications of SDF-1–derived N-terminal peptides may ameliorate their binding and viral blocking properties without generating significant unspecific side effects." @default.
• W2275564897 created "2016-06-24" @default.
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• W2275564897 date "2001-06-01" @default.
• W2275564897 modified "2023-10-02" @default.
• W2275564897 title "Pharmacological Properties of Peptides Derived from Stromal Cell-Derived Factor 1: Study on Human Polymorphonuclear Cells" @default.
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• W2275564897 doi "https://doi.org/10.1124/mol.59.6.1418" @default.
• W2275564897 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11353801" @default.
• W2275564897 hasPublicationYear "2001" @default.
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