In silico-based approach to investigate the ability of PEGylated rapamycin to inhibit Galectin-3

Galectin-3 (Gal-3) is a binding protein known to play a role in cancer and fibrosis, also implicated in various diseases of lung, liver, kidney, and heart. In this study, we have investigated the ability of modified rapamycin (RP) to bind to the carbohydrate recognition domain of Gal-3. Briefly, var...

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Bibliographic Details
Published inCurrent drug discovery technologies
Main Authors Abdelkarim Maki, Marwan Abdelmahmoud, Kumar, Palanirajan Vijayaraj, Elumalai, Manogaran, Bayazeid, Omer
Format Journal Article
LanguageEnglish
Published United Arab Emirates 22.01.2020
Subjects
PEGylation
Molecular modeling
Rapamycin
Galectin-3
Everolimus
Cancer
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Summary:Galectin-3 (Gal-3) is a binding protein known to play a role in cancer and fibrosis, also implicated in various diseases of lung, liver, kidney, and heart. In this study, we have investigated the ability of modified rapamycin (RP) to bind to the carbohydrate recognition domain of Gal-3. Briefly, various molecular weights of methoxy polyethylene glycols (MPEG) were conjugated with RP to obtain RP-MPEG compounds with molecular weights of 1002.29, 1090.40, 1178.51, 1266.6 and 1354.72 g/mol. Furthermore, the molecules were docked with Gal-3 using MOE.2014 software. According to the results obtained from the molecular modeling algorithm based on shape complementarity principles, RP-MPEG with the molecular weight of 1178.51 g/mol and a logP value of 3.79 has the best affinity for a non-carbohydrate-based Gal-3 inhibitor. Moreover, in vitro hemagglutination assay results revealed that RP analog, everolimus, has possessed potent agglutination inhibition with a minimum inhibitory concentration of 160.77 ± 2.52 μg/mL, which suggested that RP derivatives are potential Gal-3 inhibitors.
ISSN:1875-6220