We have recently described a biochemical detection method for peptide products of enzymatic reactions based on the formation of PDZ domain·peptide ligand complexes. The product sensor is based on using masked or cryptic PDZ domain peptide ligands as enzyme substrates. Upon enzymatic processing, a PDZ-binding motif is exposed, and the product sequence bound specifically by a Euchelate-labeled GS...

Five different peptides (P1: 84-95; P2: 152-166; P3: 52-63; P4: 7-23; P5: 110-123) homologous to relatively hydrophilic regions of human erythropoietin (huEpo) have been synthesized to identify biologically active domains of the hormone. All peptides were able to induce high titers of peptide-specific antibodies in rabbits. Antisera from rabbits induced by recombinant huEpo (rhuEpo) contained a...

This paper characterizes the potential of novel hexameric peptide ligands for on-line IgG detection in bioprocesses. Surface Plasmon Resonance (SPR) was used to study the binding of human IgG to the hexameric peptide ligand HWRGWV, which was covalently grafted to alkanethiol self-assembled monolayers (SAM) on gold surfaces. Peptide coupling on SAMs was verified, followed by covalent grafting of...

Abstract Rheumatoid arthritis (RA) is among the major human autoimmune diseases, and it affects over 1 percent of population. Although many anti-arthritis drugs are available for RA therapy, their long-term use may lead to severe adverse effects. This, combined with high cost newer drugs, poses a hurdle effective control as well patient compliance therapeutic regimens. Therefore, novel treatmen...

Integrin heterodimers undergo a conformational change upon the binding of ligand to their extracellular domains. An anti-β1 integrin monoclonal antibody AG89 can detect such a conformational change since it recognizes a ligandinducible epitope in the stalk-like region of β1 subunits. The binding of a 125I-labeled AG89 Fab fragment to α5β1 integrins on K562 cells was assessed and analyzed by the...

Human protein disulphide isomerase (hPDI) is an endoplasmic reticulum (ER) based isomerase and folding chaperone. Molecular detail of ligand recognition and specificity of hPDI are poorly understood despite the importance of the hPDI for folding secreted proteins and its implication in diseases including cancer and lateral sclerosis. We report a detailed study of specificity, interaction and di...

GLP-1 (glucagon-like peptide-1) is an incretin released from intestinal L-cells in response to food intake. Activation of the GLP-1 receptor potentiates the synthesis and release of insulin from pancreatic beta-cells in a glucose-dependent manner. The GLP-1 receptor belongs to class B of the G-protein-coupled receptors, a subfamily characterized by a large N-terminal extracellular ligand bindin...

Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived f...

Signal transduction events are often mediated by small protein domains such as SH2 (Src homology 2) domains that recognize phosphotyrosines (pY) and flanking sequences. In case of the SHP-2 receptor tyrosine phosphatase an N-terminal SH2 domain binds and inactivates the phosphatase (PTP) domain. The pY-peptide-binding site on the N-terminal SH2 domain does not overlap with the PTP binding regio...

We synthesized polymers displaying multiple copies of a peptide from the cystic fibrosis transmembrane conductance regulator (residues 108-117). This peptide is the minimal sequence needed for binding of Pseudomonas aeruginosa. Using an in vitro bacterial internalization assay, our preliminary results indicate that such a polyvalent ligand can prevent P. aeruginosa from attaching to (and being ...