Publication:
Glycodendropeptides stimulate dendritic cell maturation and T cell proliferation: a potential influenza A virus immunotherapy

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Date

2015-10

Authors

Mascaraque, Ainhoa
Kowalczyk, Wioleta
Fernández, Tahia
Palomares, Francisca
Mayorga, Cristobalina
Andreu, David
Rojo, Javier

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Royal Society of Chemistry
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Abstract

Mannosylation facilitates uptake and internalization of immunogenic peptides by antigen-processing cells expressing mannose receptors at their surface, such as DC-SIGN, a lectin that plays a key role in the immune response against different pathogens. This internalization, processing and subsequent MHC presentation may result in a strong T cell stimulation. Here, we hypothesized that combining mannose glycodendrons with multivalent presentation of peptide epitopes in a likewise dendron format would yield hybrid constructs, named glycodendropeptides (GDPs), with the capacity to enhance peptide immunogenicity, hence providing a novel and versatile platform for applications in immunotherapy. Thus, GDPs of different valencies displaying the NP366–374 epitope, a conserved sequence from the influenza A virus nucleoprotein (NP), have been built by two click chemistry-based methodologies and assessed as potential flu vaccine candidates. Preliminary evaluation of the ability of these constructs to stimulate dendritic cell maturation and lymphocyte proliferation was promising, showing the highest-functionalized NP366–374 GDPs as inducing the strongest immunostimulatory effect.

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Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Glycoproteins::Cell Adhesion Molecules
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Technology, Pharmaceutical::Click Chemistry
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Conserved Sequence
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Delivery Systems::Drug Carriers::Dendrimers
Medical Subject Headings::Anatomy::Cells::Epithelial Cells::Dendritic Cells
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Epitopes
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Lectins, C-Type
Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Mannose
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Mannose-Binding Lectins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nucleoproteins::RNA-Binding Proteins
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes
Medical Subject Headings::Chemicals and Drugs::Complex Mixtures::Biological Agents::Vaccines
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Viral Proteins::Viral Structural Proteins::Nucleocapsid Proteins::Viral Core Proteins

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Keywords

Moléculas de adhesión celular, Química clic, Secuencia conservada, Dendrímeros, Células dendríticas, Epítopos, Inmunoterapia, Lectinas tipo C, Manosa, Lectinas de unión a manosa, Péptidos, Proteínas de unión al ARN, Receptores de superficie celular, Linfocitos T, Vacunas, Proteínas del centro vírico

Citation

Masqueraque A, Kowalczyk V, Fernández T. Palomares F,Mayorga C, Andreu D. Glycodendropeptides stimulate dendritic cell maturtion and T cell proliferation: a potential influenza A virus immunotherapy. MedChemComm. 2015; 6. 1755-1760.