Design, Synthesis, and Preliminary Biological Evaluation of GlcNAc‐6P Analogues for the Modulation of Phosphoacetylglucosamine Mutase 1 (AGM1/PGM3)

A library of GlcNAc 6‐ or 1‐phosphate analogues was designed, and each compound was evaluated computationally through docking studies for its binding affinity to AGM1/PGM3. The compounds with the highest binding affinity, as ranked through a docking score, were synthesised and screened for their abi...

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Bibliographic Details
Published inEuropean journal of organic chemistry Vol. 2018; no. 17; pp. 1946 - 1952
Main Authors Paiotta, Alice, D'Orazio, Giuseppe, Palorini, Roberta, Ricciardiello, Francesca, Zoia, Luca, Votta, Giuseppina, De Gioia, Luca, Chiaradonna, Ferdinando, La Ferla, Barbara
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 08.05.2018
Wiley Subscription Services, Inc
Subjects
Affinity
Binding
Carbohydrates
Chemistry
Chemistry, Organic
Computational chemistry
Docking
Drug design
Enzymes
Glycomimetics
Inhibitors
Physical Sciences
Science & Technology
Glycomimetics
Carbohydrates
Enzymes
Computational chemistry
Inhibitors
DOCKING
Drug design
GLYCOSYLATION
PROTEINS
DERIVATIVES
DISCOVERY
TRANSFERASE
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Summary:A library of GlcNAc 6‐ or 1‐phosphate analogues was designed, and each compound was evaluated computationally through docking studies for its binding affinity to AGM1/PGM3. The compounds with the highest binding affinity, as ranked through a docking score, were synthesised and screened for their ability to inhibit the production of UDP‐GlcNAc. A glycofused oxazoline analogue showed good inhibition, and gave significant results in vitro. A potential lead compound, able to inhibit the biosynthesis of UDP‐GlcNAc, was identified through computational screening. The compound was synthesised, and its activity was evaluated through an in‐vitro assay.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201800183