Chameleon sequences, nanoparticle conjugation and immunogenicity of a protein

What is it about?

Using MPT63 as a model, we show that the conjugation of a nanoparticle leads to a switch between beta sheet and alpha helix resulting in compromised immunogenicity of the protein. The switch is controlled by the chameleon sequences, and triggered by relatively small scale energy variation. Careful optimization of the sequence can reverse the effect of nanoparticle induced conformation switch. We emphasize that the development of a nanoparticle conjugated protein pharmaceutical needs careful optimization of the protein-nanoparticle interaction, the sequence factors and solution conditions.

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Why is it important?

Nanoparticle conjugated biologics are gaining lot of attentions. This study emphasizes that the consideration of protein-nanoparticle interaction and the resulting effect on protein conformational switch needs careful optimization to develop an active product.