Idiotype specific peptides bind to the surface immunoglobulins of two murine B-cell lymphoma lines, inducing signal transduction.
Using a random combinatorial synthetic peptide library method based on a one-bead one-peptide concept for ligand identification (Lam et. al, Nature 1991, 354, 82-84.), idiotype specific peptides were retrieved and optimized for interaction with the cell surface immunoglobulins [IgM(kappa)] of two murine B lymphoma cell lines. Several of the identified peptides were characterized with respect to cell binding and signal transduction. These peptides were able to bind specifically to the surface immunoglobulins of these lymphoma cells. In addition to binding, when synthesized in tetrameric or multimeric forms, the peptides were able to trigger signal transduction resulting in an increase in protein tyrosine phosphorylation. Since D-amino acid peptide libraries were used in some of our efforts to identify binding ligands, several of the idiotype-specific peptides are composed of all D-amino acids (e.g. wGeyvmvnG). These findings may have important therapeutic implications for targeted-therapy of B-cell lymphoma as these D-amino acid ligands are more resistant to proteolysis resulting in a prolonged pharmacokinetic disposition in vivo.
Lam
K S
KS
Arizona Cancer Center, Department of Medicine, USA.
Lou
Q
Q
Zhao
Z G
ZG
Smith
J
J
Chen
M L
ML
Pleshko
E
E
Salmon
S E
SE
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D016384:Consensus Sequence; D007145:Immunoglobulin kappa-Chains / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007145:Immunoglobulin kappa-Chains; D008024:Ligands; D009842:Oligopeptides