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• W2015622018 endingPage "490" @default.
• W2015622018 startingPage "477" @default.
• W2015622018 abstract "Fusion proteins containing immunoglobulin Fc domains attached to bioactive moieties have been developed as therapeutic agents against several diseases. Here, we describe the development and characteristics of a novel fusion protein (FLSC R/T–IgG1) that targets CCR5, the major coreceptor for HIV-1 during primary infection. FLSC R/T–IgG1 was expressed from a synthetic gene that linked a single chain gp120–CD4 complex containing an R5 gp120 sequence with the hinge–CH2–CH3 portion of human immunoglobulin γ subtype 1. Purified FLSC R/T–IgG1 exhibited a molecular mass of 189 kDa under reducing conditions, which matched the expected size of one polypeptide chain. Chemically crosslinked or untreated FLSC R/T–IgG1 exhibited a mass of a 360-kDa polypeptide under reducing and nonreducing conditions, which indicated that the molecule adopts a disulfide-linked bivalent structure. The chimeric molecule bound specifically to CCR5-expressing cells and to peptides derived from the CCR5 N-terminus. Such binding was more efficient than what was obtained with a monomeric single chain gp120–CD4 complex. FLSC R/T–IgG1 binding to CCR5 was blocked by preincubation of coreceptor-expressing cells with CCR5 ligands and by antibody to the coreceptor binding domain of gp120. Conversely, FLSC R/T–IgG1 blocked the binding of chemokine to CCR5. However, FLSC R/T–IgG1 did not trigger intracellular Ca2+ mobilization in peripheral blood mononuclear cells. FLSC R/T–IgG1 potently neutralized primary R5 HIV-1 in both a PBMC-based assay and cell line-based assays but did not affect the replication of X4 viruses. These findings suggest that FLSC R/T–IgG1 might be used as a possible therapeutic agent against HIV." @default.
• W2015622018 created "2016-06-24" @default.
• W2015622018 creator A5030545878 @default.
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• W2015622018 creator A5061216308 @default.
• W2015622018 date "2006-06-01" @default.
• W2015622018 modified "2023-10-08" @default.
• W2015622018 title "An Immunoglobulin Fusion Protein Based on the gp120-CD4 Receptor Complex Potently Inhibits Human Immunodeficiency Virus Type 1<i>in Vitro</i>" @default.
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