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Expert Opin Drug Discov. 2019 Feb 5:1-9. doi: 10.1080/17460441.2019.1573813. [Epub ahead of print]

Carbohydrate-protein interactions and multivalency: implications for the inhibition of influenza A virus infections.

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1
a Department of Chemical Biology & Drug Discovery , Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , The Netherlands.

Abstract

Protein-carbohydrate interactions play a very important role in many biological processes. A single interaction between a protein and a carbohydrate is usually weak, but multivalent ligands can compensate for this deficiency by binding multiple binding sites to one biological entity simultaneously. Over the past few years, numerous efforts have been made for the design and synthesis of carbohydrate-based multivalent ligands thereby serving as potent inhibitors for pathogens such as the influenza A virus. Areas covered: In this review, the authors cover a variety of multivalent systems from small to large molecules which showed a potent inhibitory effect against several pathogens. Expert opinion: Scaffold structure, linker type, and ligand density are important parameters that need to be optimized for potent multivalent inhibitors. The challenges of multivalent glycodrugs include issues such as bioavailability, pharmacokinetics, and immunogenicity which greatly depend on where the compounds are used in the body. Anti-flu (influenza) applications in the lungs using multivalent carbohydrates particularly has potential because of the high binding affinities. With much more research focusing on Influenza A virus inhibition, therapeutic applications may be achieved in the near future.

KEYWORDS:

Carbohydrate-protein interactions; hemagglutinin; influenza A virus; multivalent inhibitors

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