Presentation of epitopes on genetically engineered peptides and selection of lymphoma-targeting moieties based on epitope biorecognition.
A His-tagged coiled coil stem loop peptide with stable secondary structure was designed and biosynthesized. A series of oligopeptides related to the EBV envelope glycoprotein 350/220 N-terminal nonapeptide as potential CD21 receptor-binding epitopes were engineered into the loop region of the peptide scaffold. It was shown that these peptides had a stable alpha-helical coiled coil structure and assumed a monomeric form in PBS. Biorecognition of the epitopes was studied by immobilizing the epitope-containing peptides on complexed Ni2+-containing surfaces through His-Ni2+ chelation and incubating with purified soluble CD21 receptor or CD21+ cells. The results showed that the potential epitopes bound to CD21 and CD21+ cells at different affinities depending on oligopeptide structures. This approach allows for the evaluation of epitope biorecognizabilities and the selection of optimal oligopeptides among sequences for use as targeting moieties in the design of new lymphoma-targeting polymeric drug carriers.
Tang
Aijun
A
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Kopecek
Jindrich
J
D000951:Antigens, Neoplasm / Q000276:immunology; D001483:Base Sequence; D016503:Drug Delivery Systems; D000939:Epitopes; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D017433:Protein Structure, Secondary; D017464:Receptors, Complement 3d / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000951:Antigens, Neoplasm; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D010446:Peptide Fragments; D010455:Peptides; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins