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Chemical Structure| 688744-20-9 Chemical Structure| 688744-20-9

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Chemical Structure| 688744-20-9

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Cifone, Matthew T. ; He, YongLe ; Basu, Rajeswari ; Wang, Nan ; Davoodi, Shabnam ; Spagnuolo, Lauren A. , et al.

Abstract: The relationship between drug-target residence time and the post-antibiotic effect (PAE) provides insights into target vulnerability. To probe the vulnerability of bacterial acetyl-CoA carboxylase (ACC), a series of heterobivalent inhibitors were synthesized based on pyridopyrimidine 1 and moiramide B (3) which bind to the biotin carboxylase and carboxyltransferase ACC active sites, resp. The heterobivalent compound 17, which has a linker of 50 Å, was a tight binding inhibitor of Escherichia coli ACC (Kiapp 0.2 nM) and could be displaced from ACC by a combination of both 1 and 3 but not just by 1. In agreement with the prolonged occupancy of ACC resulting from forced proximity binding, the heterobivalent inhibitors produced a PAE in E. coli of 1-4 h in contrast to 1 and 3 in combination or alone, indicating that ACC is a vulnerable target and highlighting the utility of kinetic, time-dependent effects in the drug mechanism of action.

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Product Details of [ 688744-20-9 ]

CAS No. :688744-20-9
Formula : C8H8Br2O
M.W : 279.96
SMILES Code : CC1=C(Br)C(OC)=CC=C1Br

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