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Design and synthesis of thiamine analogues to study their binding to the ECF transporter for thiamine in bacteria

Monjas, L., Swier, L. J. Y. M., de Voogd, A. R., Oudshoorn, R. C., Hirsch, A. K. H. & Slotboom, D. J., 2016, In : MedChemCommun. 7, 5, p. 966-971 6 p.

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  • Design and synthesis of thiamine analogues to study their binding to the ECF

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DOI

Energy-coupling factor (ECF) transporters mediate the uptake of vitamins in bacteria. Given that these ECF transporters are not present in eukaryotic cells, they represent an interesting target for the development of novel antibiotics. Here, we present the design and synthesis of compounds that bind to ThiT, the substrate-binding domain of the ECF transporter for thiamine from Lactococcus lactis. We modified the methyl substituent of the pyrimidine ring of thiamine, in order to evaluate its contribution to the binding affinity. Our results indicate that as long as a hydrophobic substituent is maintained, the high binding affinity is almost unchanged, opening up opportunities for the design of selective compounds.

Original languageEnglish
Pages (from-to)966-971
Number of pages6
JournalMedChemCommun
Volume7
Issue number5
Publication statusPublished - 2016

    Keywords

  • COUPLING FACTOR TRANSPORTER, HYDE SCORING FUNCTION, DEHYDROGENASE COMPLEX, ABC TRANSPORTERS, STRUCTURAL BASIS, S-COMPONENT, MECHANISM, PHOSPHORYLATION, SPECIFICITY

ID: 33262915