Anti‐Carbohydrate Antibodies Elicited by Polyvalent Display on a Viral Scaffold

Kaltgrad, Eiton; Gupta, Sayam Sen; Punna, Sreenivas; Huang, Chien Jung; Chang, Aileen Y.; Wong, Chi‐Huey; Finn, M. G.; Blixt, Ola

doi:10.1002/cbic.200700225

Cited by 85 publications

(74 citation statements)

References 57 publications

(25 reference statements)

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“…Similar conditions were used to functionalize CPMV with Gd complexes for magnetic resonance imaging, [22] glycopolymers for polyvalent binding to cell-surface lectins, [23] and various carbohydrates to elicit anticarbohydrate antibodies. [24] The group of Carrico has also relied on the BPDS/CuBr system for the chemoselective modification of a human adenovirus type 5 (hAd5, metabolically labeled with azido sugars) with a FLAG peptide, fluorophores, and the cancer-selective ligand folate. The folate-decorated hAd5 has demonstrated a significant increase in transgene delivery to murine breast cancer cells.…”

Section: Efficient and Benign Cuaac Bioconjugation Procedures Developmentioning

confidence: 99%

Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide–Alkyne Cycloadditions

2011

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The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been established as a powerful coupling technology for the conjugation of proteins, nucleic acids, and polysaccharides. Nevertheless, several shortcomings related to the presence of Cu, mainly oxidative degradation by reactive oxygen species and sample contamination by Cu, have been pointed out. This Minireview discusses key aspects found in the development of the efficient and benign functionalization of biomacromolecules through CuAAC, as well as the Cu-free strain-promoted azide-alkyne cycloaddition (SPAAC).

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Section: Efficient and Benign Cuaac Bioconjugation Procedures Developmentioning

confidence: 99%

Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide–Alkyne Cycloadditions

2011

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“…Several recent studies have used viruses and virus-like particles as immunogenic scaffolds for a variety of molecules including glycans. [38][39][40][41] The requirements for viral self-assembly of rigidity and symmetry result in regular spacing of fixed, chemically accessible groups, thus making these platforms ideal for multivalent attachment of oligosaccharide determinants. Oligosaccharide cluster density is increasingly recognized as a major determinant for immunological discrimination between self and non-self CHO antigens.…”

Section: Filamentous Phage As a Carrier For Carbohydrate Haptensmentioning

confidence: 99%

Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen

et al. 2011

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Filamentous bacteriophage are commonly used as immunogenic carriers for peptides and proteins displayed on the phage surface. Previously, we showed that immunization with phage to which peptides had been chemically conjugated can elicit a focused anti-peptide antibody response compared with traditional carrier molecules bearing the same peptide, perhaps due to the low surface complexity of the phage. The regularity of its surface also gives the phage other advantages as a carrier, including immunological simplicity and thousands of well-defined sites for chemical conjugation. More recently, we showed that focusing of antibody responses against 'target' peptides was enhanced when the phage's molecular surface was simplified by removal of immunodominant B-cell epitopes present on the minor coat protein, pIII. The pIII-truncated variant elicits an antibody response that is largely restricted to the exposed N-terminus of the major coat protein, pVIII, and to phage-associated bacterial lipopolysaccharide, and a significant fraction of this response crossreacts with a 12-residue peptide covering the surface-exposed region of pVIII. This allows one to track antibody responses against the phage (and any associated haptens) as they develop over time, and characterize them using a combination of serological, flow cytometric, cellular and immunogenetic assays. The filamentous phage thus provides an excellent model system for studying various aspects of the antibody response, all with the goal of targeting antibody production against weakly immunogenic peptides, proteins and carbohydrates.

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“…In particular, the regioprecision of surface functionalization can be crucial for many biomedical applications. For example, in their recent endeavor, the Finn group exploited the architectural features of the virus to explore how spatial distribution and polyvalent display of antigenic carbohydrates would modulate the mammalian immune response [67]. Moreover, a new way to enhance carbohydrate immunogenicity has been reported by means of ordered display on the surface of the CPMV capsid [68,69].…”

Section: Chemical Modification In Combination With Genetic Mutationmentioning

confidence: 99%

Viruses and virus-like protein assemblies—Chemically programmable nanoscale building blocks

2009

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Supramolecular proteins are generated using a limited set of twenty amino acids, but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite threedimensional structures. Viruses, virus-like particles, ferritins, enzyme complexes, cellular micro-compartments, and other supramolecular protein assemblies exemplify these systems, with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging, metal storage, catalysis or sequestering reactions at the nanometer scale. These versatile protein systems, dubbed as bionanoparticles (BNPs), have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications. Here, we focus on some of the key modifi cation strategies that have been utilized, ranging from basic protein conjugation techniques to more novel strategies, to expand the functionalities of these multimeric protein assemblies. Ultimately, in combination with molecular cloning and sophisticated chemistries, these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.

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Anti‐Carbohydrate Antibodies Elicited by Polyvalent Display on a Viral Scaffold

Cited by 85 publications

References 57 publications

Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide–Alkyne Cycloadditions

Reliable and Efficient Procedures for the Conjugation of Biomolecules through Huisgen Azide–Alkyne Cycloadditions

Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen

Viruses and virus-like protein assemblies—Chemically programmable nanoscale building blocks

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