| Structural highlights
3sqy is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Ligands: | , |
Related: | 3sr5, 3srq, 3srr, 3srs, 3sru, 3srw |
Gene: | folA (Staphylococcus aureus) |
Activity: | Dihydrofolate reductase, with EC number 1.5.1.3 |
Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains.
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines.,Li X, Hilgers M, Cunningham M, Chen Z, Trzoss M, Zhang J, Kohnen L, Lam T, Creighton C, Gc K, Nelson K, Kwan B, Stidham M, Brown-Driver V, Shaw KJ, Finn J Bioorg Med Chem Lett. 2011 Sep 15;21(18):5171-6. Epub 2011 Jul 23. PMID:21831637[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li X, Hilgers M, Cunningham M, Chen Z, Trzoss M, Zhang J, Kohnen L, Lam T, Creighton C, Gc K, Nelson K, Kwan B, Stidham M, Brown-Driver V, Shaw KJ, Finn J. Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5171-6. Epub 2011 Jul 23. PMID:21831637 doi:10.1016/j.bmcl.2011.07.059
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