Glycoclusters with Additional Functionalities for Binding to the LecA Lectin from Pseudomonas aeruginosa

Anthony Angeli (1) , Lucie Dupin (2) , Mimouna Madaoui (1) , Muchen Li (2) , Gérard Vergoten (3) , Shuai Wang (4) , Albert Meyer (1) , Thomas Gehin (2) , Sébastien Vidal (4) , Jean-Jacques Vasseur (1) , Yann Chevolot (2) , François Morvan (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 INL - C&N - INL - Chimie et Nanobiotechnologies
3 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576
4 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

Due to the ability of Pseudomonas aeruginosa (PA) to develop antibiotic resistances, alternative therapeutic strategies have been proposed. Among others, carbohydrate multivalent molecules targeting lectin‐based virulent factors have been widely reported in particular those targeting LecA. LecA is a tetravalent galactose specific lectin involved in biofilm formation and cell internalization. Herein, we report the synthesis of 36 galactoclusters built from galactosides with aromatic and non‐aromatic aglycons and with an additional chain. The chains were either neutral or positively charged. Only the galactoclusters with naphthyl or tyrosine aglycon showed a moderate increase of binding for the positively charged 3‐dimethylammonium propyl chain. In contrast, the non‐aromatic galactoclusters display typically poorer binding properties towards LecA. The introduction of these side chains led to improved affinities up to becoming comparable to the high‐affinity aromatic galactoclusters.

Domains: Organic chemistry

Anthony Angeli, Lucie Dupin, Mimouna Madaoui, Muchen Li, Gérard Vergoten, et al.. Glycoclusters with Additional Functionalities for Binding to the LecA Lectin from Pseudomonas aeruginosa. ChemistrySelect, 2017, 2 (32), pp.10420-10427. ⟨10.1002/slct.201702131⟩. ⟨hal-02122269⟩