Analysis of the Binding of the Fab Fragment of Monoclonal Antibody NC10 to Influenza Virus N9 Neuraminidase from Tern and Whale Using the BIAcore Biosensor: Effect of Immobilization Level and Flow Rate on Kinetic Analysis

Kortt, Alexander A.; Nice, Edouard C.; Gruen, L.C.

doi:10.1006/abio.1999.4183

Cited by 35 publications

(16 citation statements)

References 38 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). The data were globally fit with a simple binding model (1:1 Langmuir) incorporating a mass transfer component (Glaser, 1993;Myszka et al, 1998;Kortt et al, 1999). This analysis yielded an association rate constant (k a ) (mean 6 S.D.)…”

Section: Kinetic Studies Of Gevokizumab Impact On the Il-1b Signalingmentioning

confidence: 99%

Detailed Mechanistic Analysis of Gevokizumab, an Allosteric Anti–IL-1βAntibody with Differential Receptor-Modulating Properties

Issafras

Corbin

Goldfine

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Interleukin-1b (IL-1b) is a proinflammatory cytokine that is implicated in many autoinflammatory disorders, but is also important in defense against pathogens. Thus, there is a need to safely and effectively modulate IL-1b activity to reduce pathology while maintaining function. Gevokizumab is a potent anti-IL-1b antibody being developed as a treatment for diseases in which IL-1b has been associated with pathogenesis. Previous data indicated that gevokizumab negatively modulates IL-1b signaling through an allosteric mechanism. Because IL-1b signaling is a complex, dynamic process involving multiple components, it is important to understand the kinetics of IL-1b signaling and the impact of gevokizumab on this process. In the present study, we measured the impact of gevokizumab on the IL-1b system using Schild analysis and surface plasmon resonance studies, both of which demonstrated that gevokizumab decreases the binding affinity of IL-1b for the IL-1 receptor type I (IL-1RI) signaling receptor, but not the IL-1 counter-regulatory decoy receptor (IL-1 receptor type II). Gevokizumab inhibits both the binding of IL1b to IL-1RI and the subsequent recruitment of IL-1 accessory protein primarily by reducing the association rates of these interactions. Based on this information and recently published structural data, we propose that gevokizumab decreases the association rate for binding of IL-1b to its receptor by altering the electrostatic surface potential of IL-1b, thus reducing the contribution of electrostatic steering to the rapid association rate. These data indicate, therefore, that gevokizumab is a unique inhibitor of IL-1b signaling that may offer an alternative to current therapies for IL-1b-associated autoinflammatory diseases.

show abstract

Section: Kinetic Studies Of Gevokizumab Impact On the Il-1b Signalingmentioning

confidence: 99%

Detailed Mechanistic Analysis of Gevokizumab, an Allosteric Anti–IL-1βAntibody with Differential Receptor-Modulating Properties

Issafras

Corbin

Goldfine

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Regeneration of the Kgp surface was achieved by running the dissociation reaction to completion before the next injection of analyte. The binding data was evaluated with BIAevaluation 3.0.2 [17].…”

Section: Biosensor Binding Analysismentioning

confidence: 99%

A naturally occurring NAR variable domain binds the Kgp protease from Porphyromonas gingivalis

et al. 2002

View full text Add to dashboard Cite

The new antigen receptor (NAR) from sharks consists of a single immunoglobulin variable domain attached to five constant domains, and is hypothesised to function as an antibody. Two closely related NARs with affinity for the Kgp (lysinespecific) gingipain protease from Porphyromonas gingivalis were selected by panning an NAR variable domain library. When produced in Escherichia coli, these recombinant NARs were stable, correctly folded, and specifically bound Kgp (K d = 1.31 þ 0.26U U10 37 M). Binding localised to the Kgp adhesin domains, however without inhibiting adhesin activity. These naturally occurring proteins indicate an immune response to pathogenic bacteria and suggest that the NAR is a true antibody-like molecule. ß

show abstract

“…RIA was used to determine the concentration of biologically active binding fragment in the affinity-purified protein preparations (Baxter & Martin 1986). The binding data was evaluated with BIAevaluation 3·0·2 software (BIACORE AB) as described previously (Kortt et al 1999).…”

Section: Biosensor Binding Analysesmentioning

confidence: 99%

Ligand-binding characteristics of recombinant amino- and carboxyl-terminal fragments of human insulin-like growth factor-binding protein-3

Galanis

Firth²,

Bond³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a member of a family of structurally conserved proteins (IGFBP-1 to -6) which act as carriers and regulators of the mitogenic peptide hormones IGF-I and IGF-II. Members of the IGFBP family share conserved cysteine-rich aminoand carboxyl-terminal regions. The amino-terminal domain of these proteins is recognised to contain an IGF-binding determinant, but evidence to support a binding site in the carboxyl-terminal region of the protein is less rigorous. To further investigate this, we have synthesised both the amino-terminal (residues 1-88; N-88) and carboxyl-terminal (residues 165-264; C-165) domains of human IGFBP-3 in bacteria, as fusion proteins with a carboxyl-terminal FLAG peptide. Although only C-165 showed binding to IGF-I and -II by solutionbinding assays, both N-88 and C-165 demonstrated binding to IGF-I and -II by biosensor analysis albeit with reduced affinities compared with full-length IGFBP-3. Only the carboxyl-terminal fragment (C-165) was able to form hetero-trimeric complexes with IGF-I and the acid-labile subunit (ALS). We conclude that the carboxylterminal domain of IGFBP-3 contains an IGF-binding determinant and can form ternary complexes with ALS.

show abstract

Analysis of the Binding of the Fab Fragment of Monoclonal Antibody NC10 to Influenza Virus N9 Neuraminidase from Tern and Whale Using the BIAcore Biosensor: Effect of Immobilization Level and Flow Rate on Kinetic Analysis

Cited by 35 publications

References 38 publications

Detailed Mechanistic Analysis of Gevokizumab, an Allosteric Anti–IL-1βAntibody with Differential Receptor-Modulating Properties

Detailed Mechanistic Analysis of Gevokizumab, an Allosteric Anti–IL-1βAntibody with Differential Receptor-Modulating Properties

A naturally occurring NAR variable domain binds the Kgp protease from Porphyromonas gingivalis

Ligand-binding characteristics of recombinant amino- and carboxyl-terminal fragments of human insulin-like growth factor-binding protein-3

Contact Info

Product

Resources

About