Expanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition

Ramírez López, Pedro; Martínez Espinosa, Carlos Antonio; Merchán, Alejandro; Perona Requena, Almudena; Hernáiz Gómez-Degano, María Josefa

Expanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition

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Bioorganic Chem. 2023.pdf (5.46 MB)

Official URL

https://doi.org/10.1016/j.bioorg.2023.106913

Publication date

2023

Authors

Ramírez López, Pedro

Martínez Espinosa, Carlos Antonio

Merchán, Alejandro

Perona Requena, Almudena

Hernáiz Gómez-Degano, María Josefa

Advisors (or tutors)

Hernáiz Gómez-Degano, María Josefa

Publisher

Elsevier

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URI

https://hdl.handle.net/20.500.14352/96619

Citation

Ramírez-López P, Martínez C, Merchán A, Perona A, Hernaiz MJ. Expanding the synthesis of a library of potent glucuronic acid glycodendrons for Dengue virus inhibition. Bioorganic Chemistry 2023;141:106913. https://doi.org/10.1016/j.bioorg.2023.106913.

Abstract

Multivalent glycodendrons are valuable tools to mimic many structural and functional features of cell-surface glycoconjugates and its focal position scaffolds represent important components to increase specificity and affinity. Previous work in our group described the preparation of a tetravalent glucuronic acid dendron that binds with good affinity to Dengue virus envelope protein (KD = 22 mu M). Herein, the chemical synthesis and binding analysis of a new library of potent glucuronic acid dendrons bearing different functional group at the focal position and different level of multivalency are described. Their chemical synthesis was performed sequentially in three stages and with good yields. Namely a) the chemical synthesis of the oligo and polyalkynyl scaffolds, b) assembling with fully protected glucuronic acid-based azide units by using a microwave assisted copper-catalysed azide-alkyne cycloaddition reaction and c) sequential deprotection of hydroxyl and carboxylic acid groups. Surface Plasmon Resonance studies have demonstrated that the valency and the focal position functional group exert influence on the interaction with Dengue virus envelope protein. Molecular modelling studies were carried out in order to understand the binding observed. This work reports an efficient glycodendrons chemical synthesis that provides appropriate focal position functional group and multivalence, that offer an easy and versatile strategy to find new active compounds against Dengue virus.