Abstract
BackgroundGlycosylated proteins and lipids are important regulatory factors whose functions can be altered by addition or removal of sugars to the glycan structure. The glycans are recognized by sugar-binding lectins that serve as receptors on the surface of many cells and facilitate initiation of an intracellular signal that changes the properties of the cells. We identified a peptide that mimics the ligand of an N-acetylgalactosamine (GalNAc)-specific lectin and asked whether the peptide would express specific biological activity.FindingsA 12-mer phage display library was screened with a GalNAc-specific lectin to identify an amino acid sequence that binds to the lectin. Phage particles that were eluted from the lectin with free GalNAc were considered to have been bound to a GalNAc-binding site. Peptides were synthesized with the selected sequence as a quadravalent structure to facilitate receptor crosslinking. Treatment of human peripheral blood mononuclear cells for 24 h with the peptide stimulated secretion of interleukin-8 (IL-8) but not of IL-1β, IL-6, IL-10, or tumor necrosis factor-α (TNF-α). The secretion of IL-21 was stimulated as strongly with the peptide as with interferon-γ.ConclusionThe data indicate that the quadravalent peptide has biological activity with a degree of specificity. These effects occurred at concentrations in the nanomolar range, in contrast to free sugars that generally bind to proteins in the micro- to millimolar range.
Highlights
Glycosylated proteins and lipids are important regulatory factors whose functions can be altered by addition or removal of sugars to the glycan structure
The data indicate that the quadravalent peptide has biological activity with a degree of specificity
A phage display library was screened with a GalNAc-specific lectin as a receptor analog
Summary
Glycosylated proteins and lipids are important regulatory factors whose functions can be altered by addition or removal of sugars to the glycan structure. The glycans are recognized by sugar-binding lectins that serve as receptors on the surface of many cells and facilitate initiation of an intracellular signal that changes the properties of the cells. We identified a peptide that mimics the ligand of an N-acetylgalactosamine (GalNAc)-specific lectin and asked whether the peptide would express specific biological activity. Many cells express cell-surface receptors that bind sugarcontaining ligands and serve important regulatory functions [1]. We asked whether a peptide mimetic of N-acetylgalactosamine (GalNAc) could be identified that induces specific responses. For this purpose, a phage display library was screened with a GalNAc-specific lectin as a receptor analog. Because clusters of GalNAc bind to receptors with higher affinity than a single residue [7], and receptor crosslinking is often required for many signal transduction mechanisms [8], we designed and tested a multivalent structure containing this sequence
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